Skip to main content
SpringerLink
Log in
Book cover

NMR of Proteins and Small Biomolecules pp 69–98Cite as

NMR Studies of Metalloproteins

  • Chapter
  • First Online:

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 326))

Abstract

Metalloproteins represent a large share of the proteomes, with the intrinsic metal ions providing catalytic, regulatory, and structural roles critical to protein functions. Structural characterization of metalloproteins and identification of metal coordination features including numbers and types of ligands and metal-ligand geometry, and mapping the structural and dynamic changes upon metal binding are significant for understanding biological functions of metalloproteins. NMR spectroscopy has long been used as an invaluable tool for structure and dynamic studies of macromolecules. Here we focus on the application of NMR spectroscopy in characterization of metalloproteins, including structural studies and identification of metal coordination spheres by hetero-/homo-nuclear metal NMR spectroscopy. Paramagnetic NMR as well as 13C directly detected protonless NMR spectroscopy will also be addressed for application to paramagnetic metalloproteins. Moreover, these techniques offer great potential for studies of other non-metal binding macromolecules.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Ge R, Sun X, Gu Q et al (2007) A proteomic approach for the identification of bismuth-binding proteins in Helicobacter pylori. J Biol Inorg Chem 12:831–842

    CAS  Google Scholar 

  2. Sun XS, Tsang CN, Sun HZ (2009) Identification and characterization of metallodrug binding proteins by (metallo)proteomics. Metallomics 1:25–31

    CAS  Google Scholar 

  3. Sun HZ, Chai ZF (2010) Metallomics: an integrated science for metals in biology and medicine. Annu Rep Prog Chem A Inorg Chem 106:20–38

    CAS  Google Scholar 

  4. Waldron KJ, Robinson NJ (2009) How do bacterial cells ensure that metalloproteins get the correct metal? Nat Rev Microbiol 7:25–35

    CAS  Google Scholar 

  5. Cvetkovic A, Menon AL, Thorgersen MP et al (2010) Microbial metalloproteomes are largely uncharacterized. Nature 466:779–782

    CAS  Google Scholar 

  6. Andreini C, Bertini I, Cavallaro G et al (2008) Metal ions in biological catalysis: from enzyme databases to general principles. J Biol Inorg Chem 13:1205–1218

    CAS  Google Scholar 

  7. Lu Y, Yeung N, Sieracki N et al (2009) Design of functional metalloproteins. Nature 460:855–862

    CAS  Google Scholar 

  8. Andreini C, Bertini I, Rosato A (2009) Metalloproteomes: a bioinformatic approach. Acc Chem Res 42:1471–1479

    CAS  Google Scholar 

  9. Shu N, Zhou T, Hovmoller S (2008) Prediction of zinc-binding sites in proteins from sequence. Bioinformatics 24:775–782

    CAS  Google Scholar 

  10. Kasampalidis IN, Pitas I, Lyroudia K (2007) Conservation of metal-coordinating residues. Proteins 68:123–130

    CAS  Google Scholar 

  11. Wuthrich K (1989) Protein structure determination in solution by nuclear magnetic resonance spectroscopy. Science 243:45–50

    CAS  Google Scholar 

  12. Montelione GT, Arrowsmith C, Girvin ME et al (2009) Unique opportunities for NMR methods in structural genomics. J Struct Funct Genomics 10:101–106

    CAS  Google Scholar 

  13. Banci L, Bertini I, Luchinat C et al (2010) NMR in structural proteomics and beyond. Prog Nucl Magn Reson Spectrosc 56:247–266

    CAS  Google Scholar 

  14. Wang H, Li H, Cai B et al (2008) The effect of nitric oxide on metal release from metallothionein-3: gradual unfolding of the protein. J Biol Inorg Chem 13:411–419

    CAS  Google Scholar 

  15. Xia W, Li H, Sze KH et al (2009) Structure of a nickel chaperone, HypA, from Helicobacter pylori reveals two distinct metal binding sites. J Am Chem Soc 131:10031–10040

    CAS  Google Scholar 

  16. Tugarinov V, Muhandiram R, Ayed A et al (2002) Four-dimensional NMR spectroscopy of a 723-residue protein: chemical shift assignments and secondary structure of malate synthase G. J Am Chem Soc 124:10025–10035

    CAS  Google Scholar 

  17. Gautier A, Mott HR, Bostock MJ et al (2010) Structure determination of the seven-helix transmembrane receptor sensory rhodopsin II by solution NMR spectroscopy. Nat Struct Mol Biol 17:768–774

    CAS  Google Scholar 

  18. Sakakibara D, Sasaki A, Ikeya T et al (2009) Protein structure determination in living cells by in-cell NMR spectroscopy. Nature 458:102–105

    CAS  Google Scholar 

  19. Bertini I, Luchinat C, Parigi G et al (2005) NMR spectroscopy of paramagnetic metalloproteins. Chembiochem 6:1536–1549

    CAS  Google Scholar 

  20. Bertini I, Luchinat C, Parigi G et al (2008) Perspectives in paramagnetic NMR of metalloproteins. Dalton Trans 3782–3790

    Google Scholar 

  21. Bertini I, Luchinat C, Piccioli M (2001) Paramagnetic probes in metalloproteins. Methods Enzymol 339:314–340

    CAS  Google Scholar 

  22. Bertini I, Luchinat C (1999) New applications of paramagnetic NMR in chemical biology. Curr Opin Chem Biol 3:145–151

    CAS  Google Scholar 

  23. Ronconi L, Sadler PJ (2008) Applications of heteronuclear NMR spectroscopy in biological and medicinal inorganic chemistry. Coord Chem Rev 252:2239–2277

    CAS  Google Scholar 

  24. Rule GS, Hitchens TK (2006) Fundamentals of protein NMR spectroscopy. Springer, Dordrecht

    Google Scholar 

  25. Clore GM, Gronenborn AM (1999) In: Krishna NR, Berliner LJ (eds) Biological magnetic resonance. Kluwer Academic/Plenum Publishers, New York

    Google Scholar 

  26. Wuthrich K (2003) NMR studies of structure and function of biological macromolecules (Nobel lecture). Angew Chem Int Ed Engl 42:3340–3363

    Google Scholar 

  27. Wang H, Zhang Q, Cai B et al (2006) Solution structure and dynamics of human metallothionein-3 (MT-3). FEBS Lett 580:795–800

    CAS  Google Scholar 

  28. Capasso C, Carginale V, Crescenzi O et al (2003) Solution structure of MT_nc, a novel metallothionein from the Antarctic fish Notothenia coriiceps. Structure 11:435–443

    CAS  Google Scholar 

  29. Ge R, Watt RM, Sun X et al (2006) Expression and characterization of a histidine-rich protein, Hpn: potential for Ni2+ storage in Helicobacter pylori. Biochem J 393:285–293

    CAS  Google Scholar 

  30. Williamson MP, Craven CJ (2009) Automated protein structure calculation from NMR data. J Biomol NMR 43:131–143

    CAS  Google Scholar 

  31. Guntert P (2009) Automated structure determination from NMR spectra. Eur Biophys J 38:129–143

    Google Scholar 

  32. Lopez-Mendez B, Guntert P (2006) Automated protein structure determination from NMR spectra. J Am Chem Soc 128:13112–13122

    CAS  Google Scholar 

  33. Kuboniwa H, Grzesiek S, Delaglio F et al (1994) Measurement of HN-H alpha J couplings in calcium-free calmodulin using new 2D and 3D water-flip-back methods. J Biomol NMR 4:871–878

    CAS  Google Scholar 

  34. Dux P, Whitehead B, Boelens R et al (1997) Measurement of 15N-1H coupling constants in uniformly 15N-labeled proteins: application to the photoactive yellow protein. J Biomol NMR 10:301–306

    CAS  Google Scholar 

  35. Cornilescu G, Delaglio F, Bax A (1999) Protein backbone angle restraints from searching a database for chemical shift and sequence homology. J Biomol NMR 13:289–302

    CAS  Google Scholar 

  36. Cun S, Sun H (2010) A zinc-binding site by negative selection induces metallodrug susceptibility in an essential chaperonin. Proc Natl Acad Sci USA 107:4943–4948

    CAS  Google Scholar 

  37. Scrofani SD, Wright PE, Dyson HJ (1998) The identification of metal-binding ligand residues in metalloproteins using nuclear magnetic resonance spectroscopy. Protein Sci 7:2476–2479

    CAS  Google Scholar 

  38. Bordiga S, Bonino F, Lillerud KP et al (2010) X-ray absorption spectroscopies: useful tools to understand metallorganic frameworks structure and reactivity. Chem Soc Rev 39:4885–4927

    CAS  Google Scholar 

  39. Herrmann T, Guntert P, Wuthrich K (2002) Protein NMR structure determination with automated NOE assignment using the new software CANDID and the torsion angle dynamics algorithm DYANA. J Mol Biol 319:209–227

    CAS  Google Scholar 

  40. Legge GB, Martinez-Yamout MA, Hambly DM et al (2004) ZZ domain of CBP: an unusual zinc finger fold in a protein interaction module. J Mol Biol 343:1081–1093

    CAS  Google Scholar 

  41. Blindauer CA, Harrison MD, Parkinson JA et al (2001) A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity. Proc Natl Acad Sci USA 98:9593–9598

    CAS  Google Scholar 

  42. Arseniev A, Schultze P, Worgotter E et al (1988) Three-dimensional structure of rabbit liver [Cd7]metallothionein-2a in aqueous solution determined by nuclear magnetic resonance. J Mol Biol 201:637–657

    CAS  Google Scholar 

  43. Kagi JH (1991) Overview of metallothionein. Methods Enzymol 205:613–626

    CAS  Google Scholar 

  44. Thirumoorthy N, Manisenthil Kumar KT, Shyam Sundar A et al (2007) Metallothionein: an overview. World J Gastroenterol 13:993–996

    CAS  Google Scholar 

  45. Oz G, Pountney DL, Armitage IM (1999) In: Klaassen CD (ed) Metallothionein IV. Birkhauser Verlag, Basel

    Google Scholar 

  46. Furey WF, Robbins AH, Clancy LL et al (1986) Crystal structure of Cd, Zn metallothionein. Science 231:704–710

    CAS  Google Scholar 

  47. Palmiter RD, Findley SD, Whitmore TE et al (1992) MT-III, a brain-specific member of the metallothionein gene family. Proc Natl Acad Sci USA 89:6333–6337

    CAS  Google Scholar 

  48. Oz G, Zangger K, Armitage IM (2001) Three-dimensional structure and dynamics of a brain specific growth inhibitory factor: metallothionein-3. Biochemistry 40:11433–11441

    CAS  Google Scholar 

  49. Blindauer CA (2008) Metallothioneins with unusual residues: histidines as modulators of zinc affinity and reactivity. J Inorg Biochem 102:507–521

    CAS  Google Scholar 

  50. Berg JM, Shi Y (1996) The galvanization of biology: a growing appreciation for the roles of zinc. Science 271:1081–1085

    CAS  Google Scholar 

  51. Lee MS, Gippert GP, Soman KV et al (1989) Three-dimensional solution structure of a single zinc finger DNA-binding domain. Science 245:635–637

    CAS  Google Scholar 

  52. Stoll R, Lee BM, Debler EW et al (2007) Structure of the Wilms tumor suppressor protein zinc finger domain bound to DNA. J Mol Biol 372:1227–1245

    CAS  Google Scholar 

  53. Cornilescu CC, Porter FW, Zhao KQ et al (2008) NMR structure of the mengovirus Leader protein zinc-finger domain. FEBS Lett 582:896–900

    CAS  Google Scholar 

  54. Kotaka M, Johnson C, Lamb HK et al (2008) Structural analysis of the recognition of the negative regulator NmrA and DNA by the zinc finger from the GATA-type transcription factor AreA. J Mol Biol 381:373–382

    CAS  Google Scholar 

  55. Chou CC, Lou YC, Tang TK et al (2010) Structure and DNA binding characteristics of the three-Cys(2)His(2) domain of mouse testis zinc finger protein. Proteins 78:2202–2212

    CAS  Google Scholar 

  56. Brown RS (2005) Zinc finger proteins: getting a grip on RNA. Curr Opin Struct Biol 15:94–98

    CAS  Google Scholar 

  57. Laity JH, Lee BM, Wright PE (2001) Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol 11:39–46

    CAS  Google Scholar 

  58. Wolfe SA, Nekludova L, Pabo CO (2000) DNA recognition by Cys2His2 zinc finger proteins. Annu Rev Biophys Biomol Struct 29:183–212

    CAS  Google Scholar 

  59. Lee S, Doddapaneni K, Hogue A et al (2010) Solution structure of Gfi-1 zinc domain bound to consensus DNA. J Mol Biol 397:1055–1066

    CAS  Google Scholar 

  60. Eustermann S, Brockmann C, Mehrotra PV et al (2010) Solution structures of the two PBZ domains from human APLF and their interaction with poly(ADP-ribose). Nat Struct Mol Biol 17:241–243

    CAS  Google Scholar 

  61. Isogai S, Kanno S, Ariyoshi M et al (2010) Solution structure of a zinc-finger domain that binds to poly-ADP-ribose. Genes Cells 15:101–110

    CAS  Google Scholar 

  62. Hudson BP, Martinez-Yamout MA, Dyson HJ et al (2004) Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. Nat Struct Mol Biol 11:257–264

    CAS  Google Scholar 

  63. He Y, Imhoff R, Sahu A et al (2009) Solution structure of a novel zinc finger motif in the SAP30 polypeptide of the Sin3 corepressor complex and its potential role in nucleic acid recognition. Nucleic Acids Res 37:2142–2152

    CAS  Google Scholar 

  64. He F, Umehara T, Saito K et al (2010) Structural insight into the zinc finger CW domain as a histone modification reader. Structure 18:1127–1139

    CAS  Google Scholar 

  65. Watanabe S, Arai T, Matsumi R et al (2009) Crystal structure of HypA, a nickel-binding metallochaperone for [NiFe] hydrogenase maturation. J Mol Biol 394:448–459

    CAS  Google Scholar 

  66. Cavalli A, Salvatella X, Dobson CM et al (2007) Protein structure determination from NMR chemical shifts. Proc Natl Acad Sci USA 104:9615–9620

    CAS  Google Scholar 

  67. Shen Y, Lange O, Delaglio F et al (2008) Consistent blind protein structure generation from NMR chemical shift data. Proc Natl Acad Sci USA 105:4685–4690

    CAS  Google Scholar 

  68. Shen Y, Bryan PN, He Y et al (2010) De novo structure generation using chemical shifts for proteins with high-sequence identity but different folds. Protein Sci 19:349–356

    CAS  Google Scholar 

  69. Raman S, Huang YJ, Mao B et al (2010) Accurate automated protein NMR structure determination using unassigned NOESY data. J Am Chem Soc 132:202–207

    CAS  Google Scholar 

  70. Montalvao RW, Cavalli A, Salvatella X et al (2008) Structure determination of protein-protein complexes using NMR chemical shifts: case of an endonuclease colicin-immunity protein complex. J Am Chem Soc 130:15990–15996

    CAS  Google Scholar 

  71. Oz G, Pountney DL, Armitage IM (1998) NMR spectroscopic studies of I = 1/2 metal ions in biological systems. Biochem Cell Biol 76:223–234

    CAS  Google Scholar 

  72. Drakenberg T, Jaohansson C, Forsen S (1997) In: Reid DG (ed) Protein NMR techniques. Human Press, Totowa

    Google Scholar 

  73. Sun H (2002) Metallodrugs. In: Grant DM, Harris RK (eds) Encyclopedia of nuclear magnetic resonance: advances in NMR. Wiley, Chichester, pp 413–427

    Google Scholar 

  74. Blindauer CA, Harvey I, Bunyan KE et al (2009) Structure, properties, and engineering of the major zinc binding site on human albumin. J Biol Chem 284:23116–23124

    CAS  Google Scholar 

  75. Li H, Otvos JD (1996) 111Cd NMR studies of the domain specificity of Ag+ and Cu+ binding to metallothionein. Biochemistry 35:13929–13936

    CAS  Google Scholar 

  76. Farrell RA, Thorvaldsen JL, Winge DR (1996) Identification of the Zn(II) site in the copper-responsive yeast transcription factor, AMT1: a conserved Zn module. Biochemistry 35:1571–1580

    CAS  Google Scholar 

  77. Kakalis LT, Kennedy M, Sikkink R et al (1995) Characterization of the calcium-binding sites of calcineurin B. FEBS Lett 362:55–58

    CAS  Google Scholar 

  78. Baleja JD, Marmorstein R, Harrison SC et al (1992) Solution structure of the DNA-binding domain of Cd2-GAL4 from S. cerevisiae. Nature 356:450–453

    CAS  Google Scholar 

  79. Pan T, Coleman JE (1990) GAL4 transcription factor is not a "zinc finger" but forms a Zn(II)2Cys6 binuclear cluster. Proc Natl Acad Sci USA 87:2077–2081

    CAS  Google Scholar 

  80. Vasak M (1998) Application of 113Cd NMR to metallothioneins. Biodegradation 9:501–512

    CAS  Google Scholar 

  81. Digilio G, Bracco C, Vergani L et al (2009) The cadmium binding domains in the metallothionein isoform Cd7-MT10 from Mytilus galloprovincialis revealed by NMR spectroscopy. J Biol Inorg Chem 14:167–178

    CAS  Google Scholar 

  82. Serra-Batiste M, Cols N, Alcaraz LA et al (2010) The metal-binding properties of the blue crab copper specific CuMT-2: a crustacean metallothionein with two cysteine triplets. J Biol Inorg Chem 15:759–776

    CAS  Google Scholar 

  83. Daniels MJ, Turner-Cavet JS, Selkirk R et al (1998) Coordination of Zn2+ (and Cd2+) by prokaryotic metallothionein. Involvement of his-imidazole. J Biol Chem 273:22957–22961

    CAS  Google Scholar 

  84. Stewart AJ, Blindauer CA, Berezenko S et al (2003) Interdomain zinc site on human albumin. Proc Natl Acad Sci USA 100:3701–3706

    CAS  Google Scholar 

  85. Narula SS, Mehra RK, Winge DR et al (1991) Establishment of the metal-to-cysteine connectivities in silver-substituted yeast metallothionein. J Am Chem Soc 113:9354–9358

    CAS  Google Scholar 

  86. Andersen RJ, diTargiani RC, Hancock RD et al (2006) Characterization of the first N2S(alkylthiolate)lead compound: a model for three-coordinate lead in biological systems. Inorg Chem 45:6574–6576

    CAS  Google Scholar 

  87. Claudio ES, ter Horst MA, Forde CE et al (2000) 207Pb-1H two-dimensional NMR spectroscopy: a useful new tool for probing lead(II) coordination chemistry. Inorg Chem 39:1391–1397

    CAS  Google Scholar 

  88. Aramini JM, Hiraoki T, Yazawa M et al (1996) Lead-207 NMR: a novel probe for the study of calcium-binding proteins. J Biol Inorg Chem 1:39–48

    CAS  Google Scholar 

  89. Neupane KP, Pecoraro VL (2010) Probing a homoleptic PbS3 coordination environment in a designed peptide using 207Pb NMR spectroscopy: implications for understanding the molecular basis of lead toxicity. Angew Chem Int Ed Engl 49:8177–8180

    CAS  Google Scholar 

  90. Utschig LM, Bryson JW, O’Halloran TV (1995) Mercury-199 NMR of the metal receptor site in MerR and its protein-DNA complex. Science 268:380–385

    CAS  Google Scholar 

  91. DeSilva TM, Veglia G, Porcelli F et al (2002) Selectivity in heavy metal- binding to peptides and proteins. Biopolymers 64:189–197

    CAS  Google Scholar 

  92. Iranzo O, Thulstrup PW, Ryu SB et al (2007) The application of 199Hg NMR and 199mHg perturbed angular correlation (PAC) spectroscopy to define the biological chemistry of Hg(II): a case study with designed two- and three-stranded coiled coils. Chemistry 13:9178–9190

    CAS  Google Scholar 

  93. Utschig LM, Wright JG, Dieckmann G et al (1995) The 199Hg chemical-shift as a probe of coordination environments in blue copper proteins. Inorg Chem 34:2497–2498

    CAS  Google Scholar 

  94. Steele RA, Opella SJ (1997) Structures of the reduced and mercury-bound forms of MerP, the periplasmic protein from the bacterial mercury detoxification system. Biochemistry 36:6885–6895

    CAS  Google Scholar 

  95. Utschig LM, Baynard T, Strong C et al (1997) Probing copper-thioether coordination chemistry in rusticyanin and azurin by 2D 1H-199Hg NMR. Inorg Chem 36:2926–2927

    CAS  Google Scholar 

  96. Huffman DL, Utschig LM, O’Halloran TV (1997) Mercury-responsive gene regulation and mercury-199 as a probe of protein structure. Met Ions Biol Syst 34:503–526

    CAS  Google Scholar 

  97. Kornhaber GJ, Snyder D, Moseley HN et al (2006) Identification of zinc-ligated cysteine residues based on 13Calpha and 13Cbeta chemical shift data. J Biomol NMR 34:259–269

    CAS  Google Scholar 

  98. Kostic M, Matt T, Martinez-Yamout MA et al (2006) Solution structure of the Hdm2 C2H2C4 RING, a domain critical for ubiquitination of p53. J Mol Biol 363:433–450

    CAS  Google Scholar 

  99. Zuiderweg ER (2002) Mapping protein-protein interactions in solution by NMR spectroscopy. Biochemistry 41:1–7

    CAS  Google Scholar 

  100. Gao G, Williams JG, Campbell SL (2004) Protein-protein interaction analysis by nuclear magnetic resonance spectroscopy. Methods Mol Biol 261:79–92

    CAS  Google Scholar 

  101. Zeng YB, Zhang DM, Li H et al (2008) Binding of Ni2+ to a histidine- and glutamine-rich protein, Hpn-like. J Biol Inorg Chem 13:1121–1131

    CAS  Google Scholar 

  102. Syme CD, Viles JH (2006) Solution 1H NMR investigation of Zn2+ and Cd2+ binding to amyloid-beta peptide (Abeta) of Alzheimer’s disease. Biochim Biophys Acta 1764:246–256

    CAS  Google Scholar 

  103. Jones CE, Klewpatinond M, Abdelraheim SR et al (2005) Probing Cu2+ binding to the prion protein using diamagnetic Ni2+ and 1H NMR: the unstructured N terminus facilitates the coordination of six Cu2+ ions at physiological concentrations. J Mol Biol 346:1393–1407

    CAS  Google Scholar 

  104. Jensen MR, Hass MA, Hansen DF et al (2007) Investigating metal-binding in proteins by nuclear magnetic resonance. Cell Mol Life Sci 64:1085–1104

    CAS  Google Scholar 

  105. Schumann FH, Riepl H, Maurer T et al (2007) Combined chemical shift changes and amino acid specific chemical shift mapping of protein-protein interactions. J Biomol NMR 39:275–289

    CAS  Google Scholar 

  106. Bertini I, Das Gupta S, Hu X et al (2009) Solution structure and dynamics of S100A5 in the apo and Ca2+-bound states. J Biol Inorg Chem 14:1097–1107

    CAS  Google Scholar 

  107. Banci L, Bertini I, Ciofi-Baffoni S et al (2008) A structural-dynamical characterization of human Cox17. J Biol Chem 283:7912–7920

    CAS  Google Scholar 

  108. Banci L, Bertini I, Cantini F et al (2009) An NMR study of the interaction of the N-terminal cytoplasmic tail of the Wilson disease protein with copper(I)-HAH1. J Biol Chem 284:9354–9360

    CAS  Google Scholar 

  109. Pelton JG, Torchia DA, Meadow ND et al (1993) Tautomeric states of the active-site histidines of phosphorylated and unphosphorylated IIIGlc, a signal-transducing protein from Escherichia coli, using two-dimensional heteronuclear NMR techniques. Protein Sci 2:543–558

    CAS  Google Scholar 

  110. Lee BM, Buck-Koehntop BA, Martinez-Yamout MA et al (2007) Embryonic neural inducing factor Churchill is not a DNA-binding zinc finger protein: solution structure reveals a solvent-exposed beta-sheet and zinc binuclear cluster. J Mol Biol 371:1274–1289

    CAS  Google Scholar 

  111. Otting G (2010) Protein NMR using paramagnetic ions. Annu Rev Biophys 39:387–405

    CAS  Google Scholar 

  112. Arnesano F, Banci L, Piccioli M (2005) NMR structures of paramagnetic metalloproteins. Q Rev Biophys 38:167–219

    CAS  Google Scholar 

  113. Bertini I, Luchinat C, Rosato A (1996) The solution structure of paramagnetic metalloproteins. Prog Biophys Mol Biol 66:43–80

    CAS  Google Scholar 

  114. Otting G (2008) Prospects for lanthanides in structural biology by NMR. J Biomol NMR 42:1–9

    CAS  Google Scholar 

  115. Clore GM, Iwahara J (2009) Theory, practice, and applications of paramagnetic relaxation enhancement for the characterization of transient low-population states of biological macromolecules and their complexes. Chem Rev 109:4108–4139

    CAS  Google Scholar 

  116. Iwahara J, Tang C, Marius Clore G (2007) Practical aspects of 1H transverse paramagnetic relaxation enhancement measurements on macromolecules. J Magn Reson 184:185–195

    CAS  Google Scholar 

  117. Bertini I, Ciurli S, Dikiy A et al (2001) The first solution structure of a paramagnetic copper(II) protein: the case of oxidized plastocyanin from the cyanobacterium Synechocystis PCC6803. J Am Chem Soc 123:2405–2413

    CAS  Google Scholar 

  118. Ubbink M, Worrall JA, Canters GW et al (2002) Paramagnetic resonance of biological metal centers. Annu Rev Biophys Biomol Struct 31:393–422

    CAS  Google Scholar 

  119. Hansen DF, Led JJ (2006) Determination of the geometric structure of the metal site in a blue copper protein by paramagnetic NMR. Proc Natl Acad Sci USA 103:1738–1743

    CAS  Google Scholar 

  120. Donaldson LW, Skrynnikov NR, Choy WY et al (2001) Structural characterization of proteins with an attached ATCUN motif by paramagnetic relaxation enhancement NMR spectroscopy. J Am Chem Soc 123:9843–9847

    CAS  Google Scholar 

  121. Iwahara J, Schwieters CD, Clore GM (2004) Ensemble approach for NMR structure refinement against 1H paramagnetic relaxation enhancement data arising from a flexible paramagnetic group attached to a macromolecule. J Am Chem Soc 126:5879–5896

    CAS  Google Scholar 

  122. Yagi H, Loscha KV, Su XC et al (2010) Tunable paramagnetic relaxation enhancements by [Gd(DPA)3]3- for protein structure analysis. J Biomol NMR 47:143–153

    CAS  Google Scholar 

  123. Su XC, Otting G (2010) Paramagnetic labelling of proteins and oligonucleotides for NMR. J Biomol NMR 46:101–112

    CAS  Google Scholar 

  124. Iwahara J, Schwieters CD, Clore GM (2004) Characterization of nonspecific protein-DNA interactions by 1H paramagnetic relaxation enhancement. J Am Chem Soc 126:12800–12808

    CAS  Google Scholar 

  125. Fawzi NL, Doucleff M, Suh JY et al (2010) Mechanistic details of a protein-protein association pathway revealed by paramagnetic relaxation enhancement titration measurements. Proc Natl Acad Sci USA 107:1379–1384

    CAS  Google Scholar 

  126. Yu D, Volkov AN, Tang C (2009) Characterizing dynamic protein-protein interactions using differentially scaled paramagnetic relaxation enhancement. J Am Chem Soc 131:17291–17297

    CAS  Google Scholar 

  127. Liang B, Bushweller JH, Tamm LK (2006) Site-directed parallel spin-labeling and paramagnetic relaxation enhancement in structure determination of membrane proteins by solution NMR spectroscopy. J Am Chem Soc 128:4389–4397

    CAS  Google Scholar 

  128. Clore GM, Tang C, Iwahara J (2007) Elucidating transient macromolecular interactions using paramagnetic relaxation enhancement. Curr Opin Struct Biol 17:603–616

    CAS  Google Scholar 

  129. Tang C, Schwieters CD, Clore GM (2007) Open-to-closed transition in apo maltose-binding protein observed by paramagnetic NMR. Nature 449:1078–1082

    CAS  Google Scholar 

  130. Iwahara J, Clore GM (2006) Detecting transient intermediates in macromolecular binding by paramagnetic NMR. Nature 440:1227–1230

    CAS  Google Scholar 

  131. Volkov AN, Ubbink M, van Nuland NA (2010) Mapping the encounter state of a transient protein complex by PRE NMR spectroscopy. J Biomol NMR 48:225–236

    CAS  Google Scholar 

  132. Bertini I, Luchinat C, Parigi G (2002) Magnetic susceptibility in paramagnetic NMR. Prog Nucl Magn Reson Spectrosc 40:249–273

    CAS  Google Scholar 

  133. Biekofsky RR, Muskett FW, Schmidt JM et al (1999) NMR approaches for monitoring domain orientations in calcium-binding proteins in solution using partial replacement of Ca2+ by Tb3+. FEBS Lett 460:519–526

    CAS  Google Scholar 

  134. Banci L, Bertini I, Bren KL et al (1996) The use of peudocontact shifts to refine solution structures of paramagnetic metalloproteins: Met80Ala cyano-cytochrome c as an example. J Biol Inorg Chem 1:117–126

    CAS  Google Scholar 

  135. Goodfellow BJ, Duarte IC, Macedo AL et al (2010) An NMR structural study of nickel-substituted rubredoxin. J Biol Inorg Chem 15:409–420

    CAS  Google Scholar 

  136. Arnesano F, Banci L, Bertini I et al (2003) A strategy for the NMR characterization of type II copper(II) proteins: the case of the copper trafficking protein CopC from Pseudomonas syringae. J Am Chem Soc 125:7200–7208

    CAS  Google Scholar 

  137. Bertini I, Kursula P, Luchinat C et al (2009) Accurate solution structures of proteins from X-ray data and a minimal set of NMR data: calmodulin-peptide complexes as examples. J Am Chem Soc 131:5134–5144

    CAS  Google Scholar 

  138. Pintacuda G, Park AY, Keniry MA et al (2006) Lanthanide labeling offers fast NMR approach to 3D structure determinations of protein-protein complexes. J Am Chem Soc 128:3696–3702

    CAS  Google Scholar 

  139. Pintacuda G, John M, Su XC et al (2007) NMR structure determination of protein-ligand complexes by lanthanide labeling. Acc Chem Res 40:206–212

    CAS  Google Scholar 

  140. Nguyen TH, Ozawa K, Stanton-Cook M et al (2010) Generation of pseudocontact shifts in protein NMR spectra with a genetically encoded cobalt(II)-binding amino acid. Angew Chem Int Ed Engl 50(3):692–694

    Google Scholar 

  141. Bertini I, Del Bianco C, Gelis I et al (2004) Experimentally exploring the conformational space sampled by domain reorientation in calmodulin. Proc Natl Acad Sci USA 101:6841–6846

    CAS  Google Scholar 

  142. Bertini I, Gupta YK, Luchinat C et al (2007) Paramagnetism-based NMR restraints provide maximum allowed probabilities for the different conformations of partially independent protein domains. J Am Chem Soc 129:12786–12794

    CAS  Google Scholar 

  143. Bertini I, Duma L, Felli IC et al (2004) A heteronuclear direct-detection NMR spectroscopy experiment for protein-backbone assignment. Angew Chem Int Ed 43:2257–2259

    CAS  Google Scholar 

  144. Bermel W, Bertini I, Felli IC et al (2006) C-13-detected protonless NMR spectroscopy of proteins in solution. Prog Nucl Magn Reson Spectrosc 48:25–45

    CAS  Google Scholar 

  145. Bertini I, Jimenez B, Pierattelli R et al (2008) Protonless 13C direct detection NMR: characterization of the 37 kDa trimeric protein CutA1. Proteins 70:1196–1205

    CAS  Google Scholar 

  146. Machonkin TE, Westler WM, Markley JL (2002) 13C{13C} 2D NMR: a novel strategy for the study of paramagnetic proteins with slow electronic relaxation rates. J Am Chem Soc 124:3204–3205

    CAS  Google Scholar 

  147. Caillet-Saguy C, Delepierre M, Lecroisey A et al (2006) Direct-detected 13C NMR to investigate the iron(III) hemophore HasA. J Am Chem Soc 128:150–158

    CAS  Google Scholar 

  148. Balayssac S, Bertini I, Luchinat C et al (2006) 13C direct detected NMR increases the detectability of residual dipolar couplings. J Am Chem Soc 128:15042–15043

    CAS  Google Scholar 

  149. Bermel W, Bertini I, Felli IC et al (2003) 13C direct detection experiments on the paramagnetic oxidized monomeric copper, zinc superoxide dismutase. J Am Chem Soc 125:16423–16429

    CAS  Google Scholar 

  150. Andersson P, Weigelt J, Otting G (1998) Spin-state selection filters for the measurement of heteronuclear one-bond coupling constants. J Biomol NMR 12:435–441

    CAS  Google Scholar 

  151. Ottiger M, Delaglio F, Bax A (1998) Measurement of J and dipolar couplings from simplified two-dimensional NMR spectra. J Magn Reson 131:373–378

    CAS  Google Scholar 

  152. Duma L, Hediger S, Lesage A et al (2003) Spin-state selection in solid-state NMR. J Magn Reson 164:187–195

    CAS  Google Scholar 

  153. Meissner A, Duus JO, Sørensen OW (1997) Integration of spin-state-selective excitation into 2D NMR correlation experiments with the heteronuclear ZQ/2Q pi rotations for 1JXH- resolved E.COSY-type measurements of heteronuclear coupling constants in proteins. J Biomol NMR 10:89–94

    CAS  Google Scholar 

  154. Bermel W, Bertini I, Duma L et al (2005) Complete assignment of heteronuclear protein resonances by protonless NMR spectroscopy. Angew Chem Int Ed Engl 44:3089–3092

    CAS  Google Scholar 

  155. Bermel W, Bertini I, Felli IC et al (2006) Protonless NMR experiments for sequence-specific assignment of backbone nuclei in unfolded proteins. J Am Chem Soc 128:3918–3919

    CAS  Google Scholar 

  156. Bertini I, Felli IC, Kummerle R et al (2004) 13C-13C NOESY: an attractive alternative for studying large macromolecules. J Am Chem Soc 126:464–465

    CAS  Google Scholar 

  157. Bertini I, Felli IC, Kummerle R et al (2004) 13C-13C NOESY: a constructive use of 13C-13C spin-diffusion. J Biomol NMR 30:245–251

    CAS  Google Scholar 

  158. Arnesano F, Banci L, Bertini I et al (2003) A redox switch in CopC: an intriguing copper trafficking protein that binds copper(I) and copper(II) at different sites. Proc Natl Acad Sci USA 100:3814–3819

    CAS  Google Scholar 

  159. Madl T, Felli IC, Bertini I et al (2010) Structural analysis of protein interfaces from 13C direct-detected paramagnetic relaxation enhancements. J Am Chem Soc 132:7285–7287

    CAS  Google Scholar 

  160. Babini E, Bertini I, Capozzi F et al (2004) Direct carbon detection in paramagnetic metalloproteins to further exploit pseudocontact shift restraints. J Am Chem Soc 126:10496–10497

    CAS  Google Scholar 

  161. Bermel W, Bertini I, Felli IC et al (2010) Exclusively heteronuclear NMR experiments to obtain structural and dynamic information on proteins. ChemPhysChem 11:689–695

    CAS  Google Scholar 

  162. Kostic M, Pochapsky SS, Pochapsky TC (2002) Rapid recycle 13C\prime, 15N and 13C, 13C\prime heteronuclear and homonuclear multiple quantum coherence detection for resonance assignments in paramagnetic proteins: example of Ni2+ -containing acireductone dioxygenase. J Am Chem Soc 124:9054–9055

    CAS  Google Scholar 

  163. Bertini I, Jimenez B, Piccioli M et al (2005) Asymmetry in 13C-13C COSY spectra provides information on ligand geometry in paramagnetic proteins. J Am Chem Soc 127:12216–12217

    CAS  Google Scholar 

  164. Turano P, Lalli D, Felli IC et al (2010) NMR reveals pathway for ferric mineral precursors to the central cavity of ferritin. Proc Natl Acad Sci USA 107:545–550

    CAS  Google Scholar 

  165. Matzapetakis M, Turano P, Theil EC et al (2007) 13C–13C NOESY spectra of a 480 kDa protein: solution NMR of ferritin. J Biomol NMR 38:237–242

    CAS  Google Scholar 

  166. Williamson MP, Havel TF, Wuthrich K (1985) Solution conformation of proteinase inhibitor IIA from bull seminal plasma by 1H nuclear magnetic resonance and distance geometry. J Mol Biol 182:295–315

    CAS  Google Scholar 

  167. Kupce E, Freeman R (2008) Fast multi-dimensional NMR by minimal sampling. J Magn Reson 191:164–168

    CAS  Google Scholar 

  168. Frueh DP, Sun ZY, Vosburg DA et al (2006) Non-uniformly sampled double-TROSY hNcaNH experiments for NMR sequential assignments of large proteins. J Am Chem Soc 128:5757–5763

    CAS  Google Scholar 

  169. Marion D (2005) Fast acquisition of NMR spectra using Fourier transform of non-equispaced data. J Biomol NMR 32:141–150

    CAS  Google Scholar 

  170. Szyperski T, Yeh DC, Sukumaran DK et al (2002) Reduced-dimensionality NMR spectroscopy for high-throughput protein resonance assignment. Proc Natl Acad Sci USA 99:8009–8014

    CAS  Google Scholar 

  171. Felli IC, Brutscher B (2009) Recent advances in solution NMR: fast methods and heteronuclear direct detection. ChemPhysChem 10:1356–1368

    CAS  Google Scholar 

  172. Kim S, Szyperski T (2003) GFT NMR, a new approach to rapidly obtain precise high-dimensional NMR spectral information. J Am Chem Soc 125:1385–1393

    CAS  Google Scholar 

  173. Freeman R, Kupce E (2003) New methods for fast multidimensional NMR. J Biomol NMR 27:101–113

    CAS  Google Scholar 

  174. Kupce E, Freeman R (2004) Projection-reconstruction technique for speeding up multidimensional NMR spectroscopy. J Am Chem Soc 126:6429–6440

    CAS  Google Scholar 

  175. Schanda P, Van Melckebeke H, Brutscher B (2006) Speeding up three-dimensional protein NMR experiments to a few minutes. J Am Chem Soc 128:9042–9043

    CAS  Google Scholar 

  176. Schanda P, Brutscher B (2005) Very fast two-dimensional NMR spectroscopy for real-time investigation of dynamic events in proteins on the time scale of seconds. J Am Chem Soc 127:8014–8015

    CAS  Google Scholar 

  177. Kupce E, Freeman R (2003) Fast multi-dimensional Hadamard spectroscopy. J Magn Reson 163:56–63

    CAS  Google Scholar 

  178. Hiller S, Wasmer C, Wider G et al (2007) Sequence-specific resonance assignment of soluble nonglobular proteins by 7D APSY-NMR spectroscopy. J Am Chem Soc 129:10823–10828

    CAS  Google Scholar 

  179. Shen Y, Atreya HS, Liu G et al (2005) G-matrix Fourier transform NOESY-based protocol for high-quality protein structure determination. J Am Chem Soc 127:9085–9099

    CAS  Google Scholar 

  180. Hiller S, Garces RG, Malia TJ et al (2008) Solution structure of the integral human membrane protein VDAC-1 in detergent micelles. Science 321:1206–1210

    CAS  Google Scholar 

  181. Tugarinov V, Kay LE, Ibraghimov I et al (2005) High-resolution four-dimensional 1H-13C NOE spectroscopy using methyl-TROSY, sparse data acquisition, and multidimensional decomposition. J Am Chem Soc 127:2767–2775

    CAS  Google Scholar 

  182. Baldwin AJ, Kay LE (2009) NMR spectroscopy brings invisible protein states into focus. Nat Chem Biol 5:808–814

    CAS  Google Scholar 

  183. Bermel W, Bertini I, Felli IC et al (2009) Speeding up 13C direct detection biomolecular NMR spectroscopy. J Am Chem Soc 131:15339–15345

    CAS  Google Scholar 

  184. Lipton AS, Heck RW, Staeheli GR et al (2008) A QM/MM approach to interpreting 67Zn solid-state NMR data in zinc proteins. J Am Chem Soc 130:6224–6230

    CAS  Google Scholar 

  185. Lipton AS, Heck RW, Primak S et al (2008) Characterization of Mg2+ binding to the DNA repair protein apurinic/apyrimidic endonuclease 1 via solid-state 25Mg NMR spectroscopy. J Am Chem Soc 130:9332–9341

    CAS  Google Scholar 

Download references

Acknowledgements

This work is supported by the Research Grants Council of Hong Kong (HKU7043/06P, HKU2/06C, HKU7042/07P, HKU1/07C, HKU7038/08P, HKU7049/09P and N-HKU752/09), Croucher Foundation.

Author information

Authors and Affiliations

  1. Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China

    Hongyan Li & Hongzhe Sun

Authors
  1. Hongyan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongzhe Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hongyan Li .

Editor information

Editors and Affiliations

  1. , Dept. of Biochemistry, Hong Kong University of Science and Tech, Clear Water Bay, Hong Kong, Kowloon, China, People's Republic

    Guang Zhu

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Li, H., Sun, H. (2011). NMR Studies of Metalloproteins. In: Zhu, G. (eds) NMR of Proteins and Small Biomolecules. Topics in Current Chemistry, vol 326. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2011_214

Download citation

Publish with us

Policies and ethics

Search

Navigation