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ABPP Methodology: Introduction and Overview

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Activity-Based Protein Profiling

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 324))

Abstract

Activity-based protein profiling (ABPP) is emerging as a mature method for chemically interrogating the proteome of a cell. This chapter serves to introduce the reader to ABPP by providing overviews of the general principles of the technique, analytical methods used in ABPP, the classes of enzymes that can be specifically addressed by ABPP probes, and biological applications of ABPP.

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Abbreviations

(TOP)-ABPP:

Tandem orthogonal proteolysis ABPP

3-oxo-C12-HSL:

3-Oxo-dodecanoyl homoserine lactone

ABPP:

Activity-based protein profiling

ADP:

Adenosine diphosphate

AOMK:

Acyloxymethyl ketone

ASPP:

Active site peptide profiling

ATP:

Adenosine triphosphate

BODIPY:

Boron-dipyrromethane

CE:

Capillary electrophoresis

FDA:

Food and Drug Administration

FP:

Fluorophosphonate

HDAC:

Histone deacetylase

LC-MS:

Liquid chromatography–mass spectrometry

LIF:

Laser-induced fluorescence

ML:

Mixed lineage

MP:

Metalloprotease

MS:

Mass spectrometry

MudPIT:

Multidimensional protein identification technology

PAD4:

Protein arginine deiminase 4

PI3K:

Phosphoinositide 3-kinase

PKMT:

Protein lysine methyltransferase

PNA:

Peptide nucleic acid

RA:

Rheumatoid arthritis

SAHA:

Suberoylanilide hydroxamic acid

SAM:

S-Adenosyl-l-methionine

SDS:

Sodium dodecylsulfate

SDS-PAGE:

Sodium dodecylsulfate polyacrylamide gel electrophoresis

TEV:

Tobacco etch virus

References

  1. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    CAS  Google Scholar 

  2. Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789–799

    CAS  Google Scholar 

  3. Kobe B, Kemp BE (1999) Active site-directed protein regulation. Nature 402:373–376

    CAS  Google Scholar 

  4. Walsh CT (2006) Posttranslational modification of proteins: expanding nature’s inventory. Roberts, Englewood, CO

    Google Scholar 

  5. Gygi SP, Rist B, Gerber SA et al (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17:994–999

    CAS  Google Scholar 

  6. Washburn MP, Wolters D, Yates JR 3rd (2001) Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol 19:242–247

    CAS  Google Scholar 

  7. Zhu H, Bilgin M, Snyder M (2003) Proteomics. Annu Rev Biochem 72:783–812

    CAS  Google Scholar 

  8. Ito T, Ota K, Kubota H et al (2002) Roles for the two-hybrid system in exploration of the yeast protein interactome. Mol Cell Proteomics 1:561–566

    CAS  Google Scholar 

  9. MacBeath G (2002) Protein microarrays and proteomics. Nat Genet 32(Suppl):526–532

    CAS  Google Scholar 

  10. Evans MJ, Cravatt BF (2006) Mechanism-based profiling of enzyme families. Chem Rev 106:3279–3301

    CAS  Google Scholar 

  11. Heal WP, Dang TH, Tate EW (2011) Activity-based probes: discovering new biology and new drug targets. Chem Soc Rev 40:246–257

    CAS  Google Scholar 

  12. Cravatt BF, Wright AT, Kozarich JW (2008) Activity-based protein profiling: from enzyme chemistry to proteomic chemistry. Annu Rev Biochem 77:383–414

    CAS  Google Scholar 

  13. Bottcher T, Pitscheider M, Sieber SA (2010) Natural products and their biological targets: proteomic and metabolomic labeling strategies. Angew Chem Int Ed Engl 49:2680–2698

    Google Scholar 

  14. Barglow KT, Cravatt BF (2007) Activity-based protein profiling for the functional annotation of enzymes. Nat Methods 4:822–827

    CAS  Google Scholar 

  15. Dennehy MK, Richards KA, Wernke GR et al (2006) Cytosolic and nuclear protein targets of thiol-reactive electrophiles. Chem Res Toxicol 19:20–29

    CAS  Google Scholar 

  16. Scaloni A, Ferranti P, De Simone G et al (1999) Probing the reactivity of nucleophile residues in human 2,3-diphosphoglycerate/deoxy-hemoglobin complex by aspecific chemical modifications. FEBS Lett 452:190–194

    CAS  Google Scholar 

  17. Slaughter DE, Hanzlik RP (1991) Identification of epoxide- and quinone-derived bromobenzene adducts to protein sulfur nucleophiles. Chem Res Toxicol 4:349–359

    CAS  Google Scholar 

  18. Rando RR (1977) Mechanism-based irreversible enzyme inhibitors. Methods Enzymol 46:28–41

    CAS  Google Scholar 

  19. Drahl C, Cravatt BF, Sorensen EJ (2005) Protein-reactive natural products. Angew Chem Int Ed Engl 44:5788–5809

    CAS  Google Scholar 

  20. Pitscheider M, Sieber SA (2009) Cinnamic aldehyde derived probes for the active site labeling of pathogenesis associated enzymes. Chem Commun 2009:37413743

    Google Scholar 

  21. Weerapana E, Simon GM, Cravatt BF (2008) Disparate proteome reactivity profiles of carbon electrophiles. Nat Chem Biol 4:405–407

    CAS  Google Scholar 

  22. Evans MJ, Saghatelian A, Sorensen EJ et al (2005) Target discovery in small-molecule cell-based screens by in situ proteome reactivity profiling. Nat Biotechnol 23:1303–1307

    CAS  Google Scholar 

  23. Robinette D, Neamati N, Tomer KB et al (2006) Photoaffinity labeling combined with mass spectrometric approaches as a tool for structural proteomics. Expert Rev Proteomics 3:399–408

    CAS  Google Scholar 

  24. Tanaka Y, Bond MR, Kohler JJ (2008) Photocrosslinkers illuminate interactions in living cells. Mol Biosyst 4:473–480

    CAS  Google Scholar 

  25. Bissantz C, Kuhn B, Stahl M (2010) A medicinal chemist’s guide to molecular interactions. J Med Chem 53:5061–5084

    CAS  Google Scholar 

  26. Rostovtsev VV, Green LG, Fokin VV et al (2002) A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed Engl 41:2596–2599

    CAS  Google Scholar 

  27. Meldal M, Tornoe CW (2008) Cu-catalyzed azide-alkyne cycloaddition. Chem Rev 108:2952–3015

    CAS  Google Scholar 

  28. Speers AE, Adam GC, Cravatt BF (2003) Activity-based protein profiling in vivo using a copper(I)-catalyzed azide-alkyne [3+2] cycloaddition. J Am Chem Soc 125:4686–4687

    CAS  Google Scholar 

  29. Saxon E, Bertozzi CR (2000) Cell surface engineering by a modified Staudinger reaction. Science 287:2007–2010

    CAS  Google Scholar 

  30. Kohn M, Breinbauer R (2004) The Staudinger ligation-a gift to chemical biology. Angew Chem Int Ed Engl 43:3106–3116

    Google Scholar 

  31. Agard NJ, Prescher JA, Bertozzi CR (2004) A strain-promoted [3+2] azide-alkyne cycloaddition for covalent modification of biomolecules in living systems. J Am Chem Soc 126:15046–15047

    CAS  Google Scholar 

  32. Beatty KE, Fisk JD, Smart BP et al (2010) Live-cell imaging of cellular proteins by a strain-promoted azide-alkyne cycloaddition. Chembiochem 11:2092–2095

    CAS  Google Scholar 

  33. Codelli JA, Baskin JM, Agard NJ et al (2008) Second-generation difluorinated cyclooctynes for copper-free click chemistry. J Am Chem Soc 130:11486–11493

    CAS  Google Scholar 

  34. Amara N, Mashiach R, Amar D et al (2009) Covalent inhibition of bacterial quorum sensing. J Am Chem Soc 131:10610–10619

    CAS  Google Scholar 

  35. Liu S, Zhou B, Yang H et al (2008) Aryl vinyl sulfonates and sulfones as active site-directed and mechanism-based probes for protein tyrosine phosphatases. J Am Chem Soc 130:8251–8260

    CAS  Google Scholar 

  36. Adam GC, Sorensen EJ, Cravatt BF (2002) Proteomic profiling of mechanistically distinct enzyme classes using a common chemotype. Nat Biotechnol 20:805–809

    CAS  Google Scholar 

  37. Patricelli MP, Giang DK, Stamp LM et al (2001) Direct visualization of serine hydrolase activities in complex proteomes using fluorescent active site-directed probes. Proteomics 1:1067–1071

    CAS  Google Scholar 

  38. Liu Y, Patricelli MP, Cravatt BF (1999) Activity-based protein profiling: the serine hydrolases. Proc Natl Acad Sci USA 96:14694–14699

    CAS  Google Scholar 

  39. Kidd D, Liu Y, Cravatt BF (2001) Profiling serine hydrolase activities in complex proteomes. Biochemistry 40:4005–4015

    CAS  Google Scholar 

  40. Santoni V, Molloy M, Rabilloud T (2000) Membrane proteins and proteomics: un amour impossible? Electrophoresis 21:1054–1070

    CAS  Google Scholar 

  41. Corthals GL, Wasinger VC, Hochstrasser DF et al (2000) The dynamic range of protein expression: a challenge for proteomic research. Electrophoresis 21:1104–1115

    CAS  Google Scholar 

  42. Bottcher T, Sieber SA (2010) Showdomycin as a versatile chemical tool for the detection of pathogenesis-associated enzymes in bacteria. J Am Chem Soc 132:6964–6972

    Google Scholar 

  43. Tully SE, Cravatt BF (2010) Activity-based probes that target functional subclasses of phospholipases in proteomes. J Am Chem Soc 132:3264–3265

    CAS  Google Scholar 

  44. Jessani N, Niessen S, Wei BQ et al (2005) A streamlined platform for high-content functional proteomics of primary human specimens. Nat Methods 2:691–697

    CAS  Google Scholar 

  45. Liu H, Sadygov RG, Yates JR 3rd (2004) A model for random sampling and estimation of relative protein abundance in shotgun proteomics. Anal Chem 76:4193–4201

    CAS  Google Scholar 

  46. Old WM, Meyer-Arendt K, Aveline-Wolf L et al (2005) Comparison of label-free methods for quantifying human proteins by shotgun proteomics. Mol Cell Proteomics 4:1487–1502

    CAS  Google Scholar 

  47. Adam GC, Burbaum J, Kozarich JW et al (2004) Mapping enzyme active sites in complex proteomes. J Am Chem Soc 126:1363–1368

    CAS  Google Scholar 

  48. Okerberg ES, Wu J, Zhang B et al (2005) High-resolution functional proteomics by active-site peptide profiling. Proc Natl Acad Sci USA 102:4996–5001

    CAS  Google Scholar 

  49. Speers AE, Cravatt BF (2005) A tandem orthogonal proteolysis strategy for high-content chemical proteomics. J Am Chem Soc 127:10018–10019

    CAS  Google Scholar 

  50. Sieber SA, Mondala TS, Head SR et al (2004) Microarray platform for profiling enzyme activities in complex proteomes. J Am Chem Soc 126:15640–15641

    CAS  Google Scholar 

  51. Kodadek T (2001) Protein microarrays: prospects and problems. Chem Biol 8:105–115

    CAS  Google Scholar 

  52. Winssinger N, Ficarro S, Schultz PG et al (2002) Profiling protein function with small molecule microarrays. Proc Natl Acad Sci USA 99:11139–11144

    CAS  Google Scholar 

  53. Clark JD, Schievella AR, Nalefski EA et al (1995) Cytosolic phospholipase A2. J Lipid Mediat Cell Signal 12:83–117

    CAS  Google Scholar 

  54. Mignatti P, Rifkin DB (1996) Plasminogen activators and angiogenesis. Curr Top Microbiol Immunol 213(Pt 1):33–50

    CAS  Google Scholar 

  55. DeClerck YA, Imren S, Montgomery AM et al (1997) Proteases and protease inhibitors in tumor progression. Adv Exp Med Biol 425:89–97

    CAS  Google Scholar 

  56. Gorrell MD (2005) Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders. Clin Sci (Lond) 108:277–292

    CAS  Google Scholar 

  57. Walsh CT (1979) Enzymatic reaction mechanisms. W.H. Freeman, New York

    Google Scholar 

  58. Powers JC, Asgian JL, Ekici OD et al (2002) Irreversible inhibitors of serine, cysteine, and threonine proteases. Chem Rev 102:4639–4750

    CAS  Google Scholar 

  59. Bouma BN, Miles LA, Beretta G et al (1980) Human plasma prekallikrein. Studies of its activation by activated factor XII and of its inactivation by diisopropyl phosphofluoridate. Biochemistry 19:1151–1160

    CAS  Google Scholar 

  60. Jessani N, Humphrey M, McDonald WH et al (2004) Carcinoma and stromal enzyme activity profiles associated with breast tumor growth in vivo. Proc Natl Acad Sci USA 101:13756–13761

    CAS  Google Scholar 

  61. Jessani N, Liu Y, Humphrey M et al (2002) Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness. Proc Natl Acad Sci USA 99:10335–10340

    CAS  Google Scholar 

  62. Mahrus S, Craik CS (2005) Selective chemical functional probes of granzymes A and B reveal granzyme B is a major effector of natural killer cell-mediated lysis of target cells. Chem Biol 12:567–577

    CAS  Google Scholar 

  63. Gelb BD, Shi GP, Chapman HA et al (1996) Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science 273:1236–1238

    CAS  Google Scholar 

  64. Sloane BF, Yan S, Podgorski I et al (2005) Cathepsin B and tumor proteolysis: contribution of the tumor microenvironment. Semin Cancer Biol 15:149–157

    CAS  Google Scholar 

  65. Yan S, Sameni M, Sloane BF (1998) Cathepsin B and human tumor progression. Biol Chem 379:113–123

    CAS  Google Scholar 

  66. Shenai BR, Sijwali PS, Singh A et al (2000) Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum. J Biol Chem 275:29000–29010

    CAS  Google Scholar 

  67. Iwata Y, Mort JS, Tateishi H et al (1997) Macrophage cathepsin L, a factor in the erosion of subchondral bone in rheumatoid arthritis. Arthritis Rheum 40:499–509

    CAS  Google Scholar 

  68. Barrett AJ, Kembhavi AA, Brown MA et al (1982) L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L. Biochem J 201:189–198

    CAS  Google Scholar 

  69. Barrett AJ, Kembhavi AA, Hanada K (1981) E-64 [L-trans-epoxysuccinyl-leucyl-amido(4-guanidino)butane] and related epoxides as inhibitors of cysteine proteinases. Acta Biol Med Ger 40:1513–1517

    CAS  Google Scholar 

  70. Palmer JT, Rasnick D, Klaus JL et al (1995) Vinyl sulfones as mechanism-based cysteine protease inhibitors. J Med Chem 38:3193–3196

    CAS  Google Scholar 

  71. Shaw E (1994) Peptidyl diazomethanes as inhibitors of cysteine and serine proteinases. Methods Enzymol 244:649–656

    CAS  Google Scholar 

  72. Shaw E, Angliker H, Rauber P et al (1986) Peptidyl fluoromethyl ketones as thiol protease inhibitors. Biomed Biochim Acta 45:1397–1403

    CAS  Google Scholar 

  73. Pliura DH, Bonaventura BJ, Smith RA et al (1992) Comparative behaviour of calpain and cathepsin B toward peptidyl acyloxymethyl ketones, sulphonium methyl ketones and other potential inhibitors of cysteine proteinases. Biochem J 288(Pt 3):759–762

    CAS  Google Scholar 

  74. Fonovic M, Bogyo M (2007) Activity based probes for proteases: applications to biomarker discovery, molecular imaging and drug screening. Curr Pharm Des 13:253–261

    CAS  Google Scholar 

  75. Brady KD, Giegel DA, Grinnell C et al (1999) A catalytic mechanism for caspase-1 and for bimodal inhibition of caspase-1 by activated aspartic ketones. Bioorg Med Chem 7:621–631

    CAS  Google Scholar 

  76. Dai Y, Hedstrom L, Abeles RH (2000) Inactivation of cysteine proteases by (acyloxy)methyl ketones using S′-P′ interactions. Biochemistry 39:6498–6502

    CAS  Google Scholar 

  77. Kato D, Boatright KM, Berger AB et al (2005) Activity-based probes that target diverse cysteine protease families. Nat Chem Biol 1:33–38

    CAS  Google Scholar 

  78. Mitic N, Smith SJ, Neves A et al (2006) The catalytic mechanisms of binuclear metallohydrolases. Chem Rev 106:3338–3363

    CAS  Google Scholar 

  79. Whittaker M, Floyd CD, Brown P et al (1999) Design and therapeutic application of matrix metalloproteinase inhibitors. Chem Rev 99:2735–2776

    CAS  Google Scholar 

  80. Skiles JW, Gonnella NC, Jeng AY (2001) The design, structure, and therapeutic application of matrix metalloproteinase inhibitors. Curr Med Chem 8:425–474

    CAS  Google Scholar 

  81. Hooper NM, Turner AJ (2002) The search for alpha-secretase and its potential as a therapeutic approach to Alzheimer s disease. Curr Med Chem 9:1107–1119

    CAS  Google Scholar 

  82. Vihinen P, Kahari VM (2002) Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99:157–166

    CAS  Google Scholar 

  83. Sierevogel MJ, Pasterkamp G, de Kleijn DP et al (2003) Matrix metalloproteinases: a therapeutic target in cardiovascular disease. Curr Pharm Des 9:1033–1040

    CAS  Google Scholar 

  84. Sieber SA, Niessen S, Hoover HS et al (2006) Proteomic profiling of metalloprotease activities with cocktails of active-site probes. Nat Chem Biol 2:274–281

    CAS  Google Scholar 

  85. Saghatelian A, Jessani N, Joseph A et al (2004) Activity-based probes for the proteomic profiling of metalloproteases. Proc Natl Acad Sci USA 101:10000–10005

    CAS  Google Scholar 

  86. Chan EW, Chattopadhaya S, Panicker RC et al (2004) Developing photoactive affinity probes for proteomic profiling: hydroxamate-based probes for metalloproteases. J Am Chem Soc 126:14435–14446

    CAS  Google Scholar 

  87. Minucci S, Pelicci PG (2006) Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 6:38–51

    CAS  Google Scholar 

  88. Bolden JE, Peart MJ, Johnstone RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5:769–784

    CAS  Google Scholar 

  89. Marks PA, Breslow R (2007) Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25:84–90

    CAS  Google Scholar 

  90. Salisbury CM, Cravatt BF (2007) Activity-based probes for proteomic profiling of histone deacetylase complexes. Proc Natl Acad Sci USA 104:1171–1176

    CAS  Google Scholar 

  91. Overkleeft HS et al. (2012) Photoaffinity labeling in activity-based protein profiling. Topics in Current Chemistry. Springer, Berlin, Heidelberg. doi: 10.1007/128_2011_XXX

    Google Scholar 

  92. Manning G, Whyte DB, Martinez R et al (2002) The protein kinase complement of the human genome. Science 298:1912–1934

    CAS  Google Scholar 

  93. Elphick LM, Lee SE, Gouverneur V et al (2007) Using chemical genetics and ATP analogs to dissect protein kinase function. ACS Chem Biol 2:299–314

    CAS  Google Scholar 

  94. Krause DS, Van Etten RA (2005) Tyrosine kinases as targets for cancer therapy. N Engl J Med 353:172–187

    CAS  Google Scholar 

  95. Wymann MP, Marone R (2005) Phosphoinositide 3-kinase in disease: timing, location, and scaffolding. Curr Opin Cell Biol 17:141–149

    CAS  Google Scholar 

  96. Noble ME, Endicott JA, Johnson LN (2004) Protein kinase inhibitors: insights into drug design from structure. Science 303:1800–1805

    CAS  Google Scholar 

  97. Fedorov O, Marsden B, Pogacic V et al (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci USA 104:20523–20528

    CAS  Google Scholar 

  98. Fedorov O, Sundstrom M, Marsden B et al (2007) Insights for the development of specific kinase inhibitors by targeted structural genomics. Drug Discov Today 12:365–372

    CAS  Google Scholar 

  99. Hanks SK, Hunter T (1995) Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J 9:576–596

    CAS  Google Scholar 

  100. Zheng J, Knighton DR, ten Eyck LF et al (1993) Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MgATP and peptide inhibitor. Biochemistry 32:2154–2161

    CAS  Google Scholar 

  101. Patricelli MP, Szardenings AK, Liyanage M et al (2007) Functional interrogation of the kinome using nucleotide acyl phosphates. Biochemistry 46:350–358

    CAS  Google Scholar 

  102. Arcaro A, Wymann MP (1993) Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses. Biochem J 296(Pt 2):297–301

    CAS  Google Scholar 

  103. Yano H, Nakanishi S, Kimura K et al (1993) Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells. J Biol Chem 268:25846–25856

    CAS  Google Scholar 

  104. Breinbauer R et al. (2012) Activity Based Protein Profiling for Natural Product Target Discovery. Topics in Current Chemistry. Springer, Berlin, Heidelberg. doi: 10.1007/128_2011_XXX

    Google Scholar 

  105. Gupta V, Ogawa AK, Du X et al (1997) A model for binding of structurally diverse natural product inhibitors of protein phosphatases PP1 and PP2A. J Med Chem 40:3199–3206

    CAS  Google Scholar 

  106. Zhou L, Yu H, Chen K (2002) Relationship between microcystin in drinking water and colorectal cancer. Biomed Environ Sci 15:166–171

    Google Scholar 

  107. Goldberg J, Huang HB, Kwon YG et al (1995) Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature 376:745–753

    CAS  Google Scholar 

  108. Shreder KR, Liu Y, Nomanhboy T et al (2004) Design and synthesis of AX7574: a microcystin-derived, fluorescent probe for serine/threonine phosphatases. Bioconjug Chem 15:790–798

    CAS  Google Scholar 

  109. Lo LC, Pang TL, Kuo CH et al (2002) Design and synthesis of class-selective activity probes for protein tyrosine phosphatases. J Proteome Res 1:35–40

    CAS  Google Scholar 

  110. Kumar S, Zhou B, Liang F et al (2004) Activity-based probes for protein tyrosine phosphatases. Proc Natl Acad Sci USA 101:7943–7948

    CAS  Google Scholar 

  111. Zechel DL, Withers SG (2000) Glycosidase mechanisms: anatomy of a finely tuned catalyst. Acc Chem Res 33:11–18

    CAS  Google Scholar 

  112. Tsai CS, Li YK, Lo LC (2002) Design and synthesis of activity probes for glycosidases. Org Lett 4:3607–3610

    CAS  Google Scholar 

  113. Wicki J, Rose DR, Withers SG (2002) Trapping covalent intermediates on beta-glycosidases. Methods Enzymol 354:84–105

    CAS  Google Scholar 

  114. Vocadlo DJ, Bertozzi CR (2004) A strategy for functional proteomic analysis of glycosidase activity from cell lysates. Angew Chem Int Ed Engl 43:5338–5342

    CAS  Google Scholar 

  115. Vocadlo DJ, Hang HC, Kim EJ et al (2003) A chemical approach for identifying O-GlcNAc-modified proteins in cells. Proc Natl Acad Sci USA 100:9116–9121

    CAS  Google Scholar 

  116. Denisov IG, Makris TM, Sligar SG et al (2005) Structure and chemistry of cytochrome P450. Chem Rev 105:2253–2277

    CAS  Google Scholar 

  117. Guengerich FP, Wu ZL, Bartleson CJ (2005) Function of human cytochrome P450s: characterization of the orphans. Biochem Biophys Res Commun 338:465–469

    CAS  Google Scholar 

  118. Hughes AL, Powell DW, Bard M et al (2007) Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. Cell Metab 5:143–149

    CAS  Google Scholar 

  119. Aguiar M, Masse R, Gibbs BF (2005) Regulation of cytochrome P450 by posttranslational modification. Drug Metab Rev 37:379–404

    CAS  Google Scholar 

  120. Wright AT, Cravatt BF (2007) Chemical proteomic probes for profiling cytochrome p450 activities and drug interactions in vivo. Chem Biol 14:1043–1051

    CAS  Google Scholar 

  121. Wright AT, Song JD, Cravatt BF (2009) A suite of activity-based probes for human cytochrome P450 enzymes. J Am Chem Soc 131:10692–10700

    CAS  Google Scholar 

  122. Jones JE, Causey CP, Knuckley B et al (2009) Protein arginine deiminase 4 (PAD4): current understanding and future therapeutic potential. Curr Opin Drug Discov Devel 12:616–627

    CAS  Google Scholar 

  123. Vossenaar ER, van Venrooij WJ (2004) Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res Ther 6:107–111

    CAS  Google Scholar 

  124. Luo Y, Arita K, Bhatia M et al (2006) Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization. Biochemistry 45:11727–11736

    CAS  Google Scholar 

  125. Luo Y, Knuckley B, Lee YH et al (2006) A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. J Am Chem Soc 128:1092–1093

    CAS  Google Scholar 

  126. Stone EM, Schaller TH, Bianchi H et al (2005) Inactivation of two diverse enzymes in the amidinotransferase superfamily by 2-chloroacetamidine: dimethylargininase and peptidylarginine deiminase. Biochemistry 44:13744–13752

    CAS  Google Scholar 

  127. Slack JL, Causey CP, Luo Y et al (2011) Development and use of clickable activity based protein profiling agents for protein arginine deiminase 4. ACS Chem Biol 6:466–476

    CAS  Google Scholar 

  128. Luo Y, Knuckley B, Bhatia M et al (2006) Activity-based protein profiling reagents for protein arginine deiminase 4 (PAD4): synthesis and in vitro evaluation of a fluorescently labeled probe. J Am Chem Soc 128:14468–14469

    CAS  Google Scholar 

  129. Coux O, Tanaka K, Goldberg AL (1996) Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 65:801–847

    CAS  Google Scholar 

  130. Bogyo M, McMaster JS, Gaczynska M et al (1997) Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors. Proc Natl Acad Sci USA 94:6629–6634

    CAS  Google Scholar 

  131. Bochtler M, Ditzel L, Groll M et al (1999) The proteasome. Annu Rev Biophys Biomol Struct 28:295–317

    CAS  Google Scholar 

  132. Jackson G, Einsele H, Moreau P et al (2005) Bortezomib, a novel proteasome inhibitor, in the treatment of hematologic malignancies. Cancer Treat Rev 31:591–602

    CAS  Google Scholar 

  133. Richardson PG, Mitsiades C, Hideshima T et al (2006) Bortezomib: proteasome inhibition as an effective anticancer therapy. Annu Rev Med 57:33–47

    CAS  Google Scholar 

  134. Meng L, Kwok BH, Sin N et al (1999) Eponemycin exerts its antitumor effect through the inhibition of proteasome function. Cancer Res 59:2798–2801

    CAS  Google Scholar 

  135. Chauhan D, Catley L, Li G et al (2005) A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell 8:407–419

    CAS  Google Scholar 

  136. Baumeister W, Walz J, Zuhl F et al (1998) The proteasome: paradigm of a self-compartmentalizing protease. Cell 92:367–380

    CAS  Google Scholar 

  137. Verdoes M, Florea BI, Menendez-Benito V et al (2006) A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo. Chem Biol 13:1217–1226

    CAS  Google Scholar 

  138. Verdoes M, Willems LI, van der Linden WA et al (2010) A panel of subunit-selective activity-based proteasome probes. Org Biomol Chem 8:2719–2727

    CAS  Google Scholar 

  139. Geurink PP, Florea BI, Van der Marel GA et al (2010) Probing the proteasome cavity in three steps: bio-orthogonal photo-reactive suicide substrates. Chem Commun (Camb) 46:9052–9054

    CAS  Google Scholar 

  140. Spannhoff A, Sippl W, Jung M (2009) Cancer treatment of the future: inhibitors of histone methyltransferases. Int J Biochem Cell Biol 41:4–11

    CAS  Google Scholar 

  141. Ryu H, Lee J, Hagerty SW et al (2006) ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington’s disease. Proc Natl Acad Sci USA 103:19176–19181

    CAS  Google Scholar 

  142. Berdasco M, Ropero S, Setien F et al (2009) Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma. Proc Natl Acad Sci USA 106:21830–21835

    CAS  Google Scholar 

  143. Kurotaki N, Imaizumi K, Harada N et al (2002) Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet 30:365–366

    CAS  Google Scholar 

  144. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705

    CAS  Google Scholar 

  145. Smith BC, Denu JM (2009) Chemical mechanisms of histone lysine and arginine modifications. Biochim Biophys Acta 1789:45–57

    CAS  Google Scholar 

  146. Cole PA (2008) Chemical probes for histone-modifying enzymes. Nat Chem Biol 4:590–597

    CAS  Google Scholar 

  147. Chuikov S, Kurash JK, Wilson JR et al (2004) Regulation of p53 activity through lysine methylation. Nature 432:353–360

    CAS  Google Scholar 

  148. Huang J, Perez-Burgos L, Placek BJ et al (2006) Repression of p53 activity by Smyd2-mediated methylation. Nature 444:629–632

    CAS  Google Scholar 

  149. Subramanian K, Jia D, Kapoor-Vazirani P et al (2008) Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase. Mol Cell 30:336–347

    CAS  Google Scholar 

  150. Lee JS, Kim Y, Kim IS et al (2010) Negative regulation of hypoxic responses via induced Reptin methylation. Mol Cell 39:71–85

    CAS  Google Scholar 

  151. Binda O, Boyce M, Rush JS et al (2011) A chemical method for labeling lysine methyltransferase substrates. Chembiochem 12:330–334

    CAS  Google Scholar 

  152. Islam K, Zheng W, Yu H et al (2011) Expanding cofactor repertoire of protein lysine methyltransferase for substrate labeling. ACS Chem Biol 6(7):679–684

    CAS  Google Scholar 

  153. Peters W, Willnow S, Duisken M et al (2010) Enzymatic site-specific functionalization of protein methyltransferase substrates with alkynes for click labeling. Angew Chem Int Ed Engl 49:5170–5173

    CAS  Google Scholar 

  154. Krivtsov AV, Armstrong SA (2007) MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer 7:823–833

    CAS  Google Scholar 

  155. Tachibana M, Sugimoto K, Fukushima T et al (2001) Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J Biol Chem 276:25309–25317

    CAS  Google Scholar 

  156. Rathert P, Dhayalan A, Murakami M et al (2008) Protein lysine methyltransferase G9a acts on non-histone targets. Nat Chem Biol 4:344–346

    CAS  Google Scholar 

  157. Wozniak RJ, Klimecki WT, Lau SS et al (2007) 5-Aza-2′-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene 26:77–90

    CAS  Google Scholar 

  158. Wang R, Zheng W, Yu H et al (2011) Labeling substrates of protein arginine methyltransferase with engineered enzymes and matched S-adenosyl-L-methionine analogues. J Am Chem Soc 133:7648–7651

    CAS  Google Scholar 

  159. Shah K, Liu Y, Deirmengian C et al (1997) Engineering unnatural nucleotide specificity for Rous sarcoma virus tyrosine kinase to uniquely label its direct substrates. Proc Natl Acad Sci USA 94:3565–3570

    CAS  Google Scholar 

  160. Liu Y, Shah K, Yang F et al (1998) Engineering Src family protein kinases with unnatural nucleotide specificity. Chem Biol 5:91–101

    CAS  Google Scholar 

  161. Bishop AC, Ubersax JA, Petsch DT et al (2000) A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature 407:395–401

    CAS  Google Scholar 

  162. Adam GC, Cravatt BF, Sorensen EJ (2001) Profiling the specific reactivity of the proteome with non-directed activity-based probes. Chem Biol 8:81–95

    CAS  Google Scholar 

  163. Barglow KT, Cravatt BF (2004) Discovering disease-associated enzymes by proteome reactivity profiling. Chem Biol 11:1523–1531

    CAS  Google Scholar 

  164. Barglow KT, Cravatt BF (2006) Substrate mimicry in an activity-based probe that targets the nitrilase family of enzymes. Angew Chem Int Ed Engl 45:7408–7411

    CAS  Google Scholar 

  165. Rhee SG (2006) Cell signaling. H2O2, a necessary evil for cell signaling. Science 312:1882–1883

    Google Scholar 

  166. Terada LS (2006) Specificity in reactive oxidant signaling: think globally, act locally. J Cell Biol 174:615–623

    CAS  Google Scholar 

  167. D’Autreaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824

    Google Scholar 

  168. Poole LB, Nelson KJ (2008) Discovering mechanisms of signaling-mediated cysteine oxidation. Curr Opin Chem Biol 12:18–24

    CAS  Google Scholar 

  169. Reddie KG, Carroll KS (2008) Expanding the functional diversity of proteins through cysteine oxidation. Curr Opin Chem Biol 12:746–754

    CAS  Google Scholar 

  170. Benitez LV, Allison WS (1974) The inactivation of the acyl phosphatase activity catalyzed by the sulfenic acid form of glyceraldehyde 3-phosphate dehydrogenase by dimedone and olefins. J Biol Chem 249:6234–6243

    CAS  Google Scholar 

  171. Leonard SE, Garcia FJ, Goodsell DS et al (2011) Redox-based probes for protein tyrosine phosphatases. Angew Chem Int Ed Engl 50:4423–4427

    CAS  Google Scholar 

  172. Leonard SE, Reddie KG, Carroll KS (2009) Mining the thiol proteome for sulfenic acid modifications reveals new targets for oxidation in cells. ACS Chem Biol 4:783–799

    CAS  Google Scholar 

  173. Jessani N, Young JA, Diaz SL et al (2005) Class assignment of sequence-unrelated members of enzyme superfamilies by activity-based protein profiling. Angew Chem Int Ed Engl 44:2400–2403

    CAS  Google Scholar 

  174. Hayes BK, Varki A (1989) O-acetylation and de-O-acetylation of sialic acids. Sialic acid esterases of diverse evolutionary origins have serine active sites and essential arginine residues. J Biol Chem 264:19443–19448

    CAS  Google Scholar 

  175. Li YM, Xu M, Lai MT et al (2000) Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405:689–694

    CAS  Google Scholar 

  176. Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270

    CAS  Google Scholar 

  177. Christofk HR, Vander Heiden MG, Wu N et al (2008) Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452:181–186

    CAS  Google Scholar 

  178. Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744

    CAS  Google Scholar 

  179. Menendez JA, Lupu R (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7:763–777

    CAS  Google Scholar 

  180. Mohamed MM, Sloane BF (2006) Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer 6:764–775

    CAS  Google Scholar 

  181. Ramos-DeSimone N, Hahn-Dantona E, Sipley J et al (1999) Activation of matrix metalloproteinase-9 (MMP-9) via a converging plasmin/stromelysin-1 cascade enhances tumor cell invasion. J Biol Chem 274:13066–13076

    CAS  Google Scholar 

  182. Jessani N, Niessen S, Mueller BM et al (2005) Breast cancer cell lines grown in vivo: what goes in isn’t always the same as what comes out. Cell Cycle 4:253–255

    CAS  Google Scholar 

  183. Joyce JA, Baruch A, Chehade K et al (2004) Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5:443–453

    CAS  Google Scholar 

  184. Taubes G (2008) The bacteria fight back. Science 321:356–361

    CAS  Google Scholar 

  185. Heal WP, Tate EW (2012) On the Applications of Activity-Based Protein Profiling to Microbial Pathogenesis. Topics in Current Chemistry. Springer, Berlin, Heidelberg. doi: 10.1007/128_2011_299

    Google Scholar 

  186. Blum G, von Degenfeld G, Merchant MJ et al (2007) Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat Chem Biol 3:668–677

    CAS  Google Scholar 

  187. Jedeszko C, Sloane BF (2004) Cysteine cathepsins in human cancer. Biol Chem 385:1017–1027

    CAS  Google Scholar 

  188. Harbeck N, Alt U, Berger U et al (2001) Prognostic impact of proteolytic factors (urokinase-type plasminogen activator, plasminogen activator inhibitor 1, and cathepsins B, D, and L) in primary breast cancer reflects effects of adjuvant systemic therapy. Clin Cancer Res 7:2757–2764

    CAS  Google Scholar 

  189. Foekens JA, Kos J, Peters HA et al (1998) Prognostic significance of cathepsins B and L in primary human breast cancer. J Clin Oncol 16:1013–1021

    CAS  Google Scholar 

  190. Rayo J, Amara N, Krief P et al (2011) Live cell labeling of native intracellular bacterial receptors using aniline-catalyzed oxime ligation. J Am Chem Soc 133(19):7469–7475

    CAS  Google Scholar 

  191. Krysiak J, Breinbauer R (2012) Activity-based protein profiling for natural product target discovery. Topics in Current Chemistry. Springer, Berlin, Heidelberg. doi: 10.1007/128_2011_289

    Google Scholar 

  192. Bulaj G, Kortemme T, Goldenberg DP (1998) Ionization-reactivity relationships for cysteine thiols in polypeptides. Biochemistry 37:8965–8972

    CAS  Google Scholar 

  193. Lewis CT, Seyer JM, Carlson GM (1989) Cysteine 288: an essential hyperreactive thiol of cytosolic phosphoenolpyruvate carboxykinase (GTP). J Biol Chem 264:27–33

    CAS  Google Scholar 

  194. Knowles JR (1976) The intrinsic pKa-values of functional groups in enzymes: improper deductions from the pH-dependence of steady-state parameters. CRC Crit Rev Biochem 4:165–173

    CAS  Google Scholar 

  195. Weerapana E, Wang C, Simon GM et al (2010) Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature 468:790–795

    CAS  Google Scholar 

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Acknowledgments

M. Nodwell thanks the Alexander von Humboldt foundation for a postdoctoral fellowship. S. Sieber is supported by the Deutsche Forschungsgemeinschaft (Emmy Noether), SFB749, FOR1406, an ERC starting grant, and the Center for Integrated Protein Science Munich CIPSM.

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Nodwell, M.B., Sieber, S.A. (2011). ABPP Methodology: Introduction and Overview. In: Sieber, S. (eds) Activity-Based Protein Profiling. Topics in Current Chemistry, vol 324. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2011_302

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