Abstract
Magnetic circular dichroism (MCD) is a convenient technique for providing structural and mechanistic insight into enzymatic systems in solution. The focus of this review is on aspects of geometric and electronic structure that can be determined by MCD, and how this method can further our understanding of enzymatic mechanisms. Dinuclear Co(II) systems that catalyse hydrolytic reactions were selected to illustrate the approach. These systems all contain active sites with similar structures consisting of two Co(II) ions bridged by one or two carboxylates and a water or hydroxide. In most of these active sites one Co(II) is five-coordinate and one is six-coordinate, with differing binding affinities. It is shown how MCD can be used to determine which binding site—five or six-coordinate—has the greater affinity. Importantly, zero-field-splitting data and magnetic exchange coupling constants may be determined from the temperature and field dependence of MCD data. The relevance of these data to the function of the enzymatic systems is discussed.
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References
Anderson RA, Vallee BL (1977) Selective cobalt oxidation as a means to differentiate metal-binding sites of cobalt alkaline phosphatase. Biochem 16:4388–4393
Anderson RA, Kennedy FS, Vallee BL (1976) The effect of Mg(II) on the spectral properties of Co(II) alkaline phosphatase. Biochem 15:3710–3716
Averill BA (2003) Dinuclear hydrolases. Comp Coord Chem II 8:641–676
Benning MM, Shim H, Raushel FM, Holden HM (2001) High resolution X-ray structures of different metal-substituted forms of phosphotriesterase from Pseudomonas diminuta. Biochem 40:2712–2722
Chaudhuri P, Querbach J, Wieghardt K, Nuber B, Weiss J (1990) Synthesis, electrochemistry, and magnetic properties of binuclear cobalt complexes containing the Co2(µ-X)(µ-carboxylato) n+2 core (X=OH, Cl, or Br; n = 1–3). The crystal structures of [Co II2 (µ-ClH2CCO2)2(µ-Cl)L2]PF6 and [CoIICoIII(µ-MeCO2)2(µ-OH)L2][ClO4]2·0.5H2O (L = N,N′,N″-trimethyl-1,4,7-triazacyclononane). J Chem Soc, Dalton Trans 1:271–278
Ciurli S, Benini S, Rypniewski WR, Wilson KS, Miletti S, Mangani S (1999) Structural properties of the nickel ions in urease: novel insights into the catalytic and inhibition mechanisms. Coord Chem Rev 190–192:331–355
Daumann LJ, Comba P, Larrabee JA, Schenk G, Stranger R, Cavigliasso G, Gahan LR (2013) Synthesis, magnetic properties, and phosphoesterase activity of dinuclear cobalt(II) complexes. Inorg Chem 52:2029–2043
Daumann LJ, Schenk G, Ollis DL, Gahan LR (2014) Spectroscopic and mechanistic studies of dinuclear metallohydrolases and their biomimetic complexes. Dalton Trans 43:910–928
Desmarais W, Bienvenue DL, Bzymek KP, Petsko GA, Ringe D, Holz RC (2006) The high-resolution structures of the neutral and the low pH crystals of aminopeptidase from Aeromonas proteolytica. J Biol Inorg Chem 11:398–408
D’souza VM, Bennett B, Copik AJ, Holz RC (2000) Divalent metal binding properties of the methionyl aminopeptidase from Escherichia coli. Biochem 39:3817–3826
Ely F, Hadler KS, Gahan LR, Guddat LW, Ollis DL, Schenk G (2010) Catalytic mechanism of the hydrolytic reaction catalyzed by an organophosphate-degrading enzyme from Agrobacterium radiobacter. Biochem J 432:565–573
Ely F, Hadler KS, Mitić N, Gahan LR, Ollis DL, Plugis NM, Russo MT, Larrabee JA, Schenk G (2011) Electronic and geometric structures of the organophosphate-degrading enzyme from Agrobacterium radiobacter (OpdA). J Biol Inorg Chem 16:777–787
Foo J-L, Jackson CJ, Carr PD, Kim H-K, Schenk G, Gahan LR, Ollis DL (2010) Mutation of outer-shell residues modulates metal ion affinity in a metalloenzyme. Biochem J 429:313–321
Hadler KS, Tanifum EA, Yip SH-C, Mitić N, Guddat LW, Jackson CJ, Gahan LR, Nguyen K, Carr PD, Ollis DL, Hengge AC, Larrabee JA, Schenk G (2008) Substrate-promoted formation of a catalytically competent binuclear center and regulation of reactivity in a glycerophosphodiesterase from Enterobacter aerogenes. J Am Chem Soc 130:14129–14138
Hadler KS, Mitić N, Ely F, Hanson GR, Gahan LR, Larrabee JA, Ollis DL, Schenk G (2009) Structural flexibility enhances the reactivity of the bioremediator glycerophosphodiesterase by fine-tuning its mechanism of hydrolysis. J Am Chem Soc 131:11900–11908
Hadler KS, Mitić N, Yip SH-C, Gahan LR, Ollis DL Schenk G, Larrabee JA (2010a) Electronic structure analysis of the dinuclear metal center in the bioremediator glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes. Inorg Chem 49:2727–2734
Hadler KS, Gahan LR, Ollis DL Schenk G (2010b) The bioremediator glycerophosphodiesterase employs a non-processive mechanism for hydrolysis. J Inorg Biochem 104:211–213
Harding MJ, Briat B (1973) The electronic absorption and magnetic circular dichroism spectra of cobalt (II) bromate hexahydrate. Mol Phys 25:745–776
Holmquist B, Kaden TA, Vallee BL (1975) Magnetic circular dichroic spectra of cobalt(II) substituted metalloenzymes. Biochem 14:1454–1461
Holz RC (2002) The aminopeptidase from Aeromonas proteolytica: structure and mechanism of co-catalytic metal centers involved in peptide hydrolysis. Coord Chem Rev 232:5–26
Jackson CJ, Kim H-K, Carr PD, Liu J-W, Ollis DL (2005) The structure of an enzyme-product complex reveals the critical role of a terminal hydroxide nucleophile in the bacterial phosphotriesterase mechanism. Biochim Biphys Acta 1752:56–64
Jackson CJ, Carr PD, Liu J-W, Watt SJ, Beck JL, Ollis DL (2007) The structure and function of a novel glycerophosphodiesterase from Enterobacter aerogenes. J Mol Biol 367:1047–1062
Jackson CJ, Foo J-L, Kim H-K, Carr PD, Liu J-W, Salem G, Ollis DL (2008) In crystallo capture of a Michaelis complex and product-binding modes of a bacterial phosphotriesterase. J Mol Biol 375:1189–1196
Johansson FB, Bond AD, Nielsen UG, Moubaraki B, Murray KS, Berry KJ, Larrabee JA, McKenzie CJ (2008) Dicobalt II–II, II–III, and III–III complexes as spectroscopic models for dicobalt enzyme active sites. Inorg Chem 47:5079–5092
Johnson MK (2000) Magnetic circular dichroism spectroscopy. In: Que L (ed) Physical methods in bioinorganic chemistry. University Science Books, Sausalito, pp 233–285
Kaden TA, Holmquist B, Vallee BL (1974) Magnetic circular dichroism of Cobalt(II) complexes. Inorg Chem 13:2585–2590
Kimura E (2000) Dimetallic hydrolases and their models. Curr Opin Chem Biol 4:207–213
Kirk ML, Peariso K (2003) Recent applications of MCD spectroscopy to metalloenzymes. Curr Opin Chem Biol 7:220–227
Krzystek J, Zvyagin SA, Ozarowski A, Fiedler AT, Brunold TC, Telser J (2004) Definitive spectroscopic determination of zero-field splitting in high-spin cobalt(II). J Am Chem Soc 126:2148–2155
Larrabee JA, Alessi CM, Asiedu ET, Cook JO, Hoerning KR, Klingler LJ, Okin GS, Santee SG, Volkert TL (1997) Magnetic circular dichroism spectroscopy as a probe of geometric and electronic structure of cobalt(II)-substituted proteins: ground-state zero-field splitting as a coordination number indicator. J Am Chem Soc 119:4182–4196
Larrabee JA, Leung C-H, Moore RL, Thamrong-nawasawat T, Wessler BSH (2004) Magnetic circular diochroism and Co(II) binding studies of Escherichia coli methionyl aminopeptidase. J Am Chem Soc 126:12316–12324
Larrabee JA, Chyun S-A, Volwiler AS (2008) Magnetic circular dichroism study of a dicobalt(II) methionine aminopeptidase/fumagillin complex and dicobalt II-II and II-III model complexes. Inorg Chem 47:10499–10508
Larrabee JA, Johnson WR, Volwiler AS (2009) Magnetic circular dichroism study of a dicobalt(II) complex with mixed 5- and 6-coordination: a spectroscopic model for dicobalt(II) hydrolases. Inorg Chem 48:8822–8829
Liu S, Widom J, Kemp CW, Crews CM, Clardy J (1998) Structure of human methionine aminopeptidase-2 complexed with fumagillin. Science 282:1324–1327
Lowther WT, Matthews BW (2002) Metalloaminopeptidases: common functional themes in disparate structural surroundings. Chem Rev 102:4581–4607
Mason WR (2007) A practical guide to magnetic circular dichroism spectroscopy. Wiley, Hoboken
McCaffery AJ, Stephens PJ, Schatz PN (1967) The magnetic optical activity of d-d transitions. Octahedral chromium(III), cobalt(III), cobalt(II), nickel(II), and manganese(II) complexes. Inorg Chem 6:1614–1625
Mitić N, Smith SJ, Neves A, Guddat LW, Gahan LR, Schenk G (2006) The catalytic mechanisms of binuclear metallohydrolases. Chem Rev 106:3338–3363
Mitić N, Miraula M, Selleck C, Hadler KS, Uribe E, Pedroso MM, Schenk G (2014) Catalytic mechanisms of metallohydrolases containing two metal ions. In: Christov CZ (ed) Advances in protein chemistry and structural biology: metal-containing enzymes. Elsevier, Oxford, pp 49–81
Munih P, Moulin A, Stamper CC, Bennett B, Ringe D, Petsko GA, Holz RC (2007) X-ray crystallographic characterization of the Co(II)-substituted tris-bound form of the aminopeptidase from Aeromonas proteolytica. J Inorg Biochem 101:1099–1107
Neese F, Solomon EI (1999) MCD C-term signs, saturation behavior, and determination of band polarizations in randomly oriented systems with spin ≥1/2. Applications to S = 1/2 and S = 5/2. Inorg Chem 38:1847–1865
Ostrovsky SM, Falk K, Pelikan J, Brown DA, Tomkowicz Z, Haase W (2006) Orbital angular momentum contribution to the magneto-optical behavior of a binuclear cobalt(II) complex. Inorg Chem 45:688–694
Ostrovsky S, Tomkowicz Z, Haase W (2009) High-spin Co(II) in monomeric and exchanged coupled oligomeric structures: magnetic and magnetic circular dichroism investigations. Coord Chem Rev 253:2363–2375
Pedroso MM, Ely F, Mitić N, Carpenter MC, Gahan LR, Wilcox DE, Larrabee JL, Ollis DL, Schenk G (2014) Comparative investigation of the reaction mechanisms of organophosphate-degrading phosphotriesterases from Agrobacterium radobacter (OpdA) and Pseudomonas diminuta (OPH). J Biol Inorg Chem 198:1263–1275
Piligkos S, Slep LD, Weyhermuller T, Chaudhuri P, Bill E, Neese F (2009) Magnetic circular dichroism spectroscopy of weakly exchanged coupled transition metal dimers: a model study. Coord Chem Rev 253:2352–2362
Prescott JM, Wagner FW, Holmquist B, Vallee BL (1985) Spectral and kinetic studies of metal-substituted Aeromonas aminopeptidase: nonidentical, interacting metal-binding sites. Biochem 24:5350–5356
Schatz PN, McCaffery AJ, Suetaka W, Henning W, Ritchie AB (1966) Faraday effect of charge-transfer transitions in Fe(CN) 3−6 , MnO4 −, and CrO4 2−. J Chem Phys 45:722–734
Schenk G, Mitić N, Gahan LR, Ollis DL, McGeary RP, Guddat LW (2012) Binuclear metallohydrolases: complex mechanistic strategies for a simple chemical reaction. Acc Chem Res 45:1593–1603
Schenk G, Mitić N, Hanson GR, Comba P (2013) Purple Aacid phosphatase: a journey into the function and mechanism of a colorful enzyme. Coord Chem Rev 257:473–482
Schultz BE, Ye BH, Li XY, Chan SI (1997) Electronic paramagnetic resonance and magnetic properties of model complexes for binuclear active sites in hydrolase enzymes. Inorg Chem 36:2617–2622
Solomon EI, Pavel EG, Loeb KE, Campochiaro C (1995) Magnetic circular dichroism spectroscopy as a probe of the geometric and electronic structure of non-heme ferrous enzymes. Coord Chem Rev 144:369–460
Solomon EI, Brunold TC, Davis MI, Kemsley JN, Sang-Kyu L, Lehnert N, Neese F, Skulan AJ, Yi-Shan Y, Zhou J (2000) Geometric and electronic structure/function correlations in non-heme iron enzymes. Chem Rev 100:235–349
Solomon EI, Neidig ML, Schenk G (2003) Magnetic circular dichroism of paramagnetic species. Comp Coord Chem II 2:339–349
Stec B, Holtz KM, Kantrowitz EV (2000) A revised mechanism for the alkaline phosphatase reaction involving three metal ions. J Mol Biol 299:1303–1311
Stephens PJ (1976) Magnetic circular dichroism. Adv Chem Phys 25:197–264
Taylor JS, Lau CY, Applebury ML, Coleman JE (1973) Escherichia coli Co(II) alkaline phosphatase. J Biol Chem 248:6216–6220
Wang WL, Chai SC, Huang M, He HZ, Hurley TD, Ye QZ (2008) Discovery of inhibitors of Escherichia coli methionine aminopeptidase with the Fe(II)-form selectivity and antibacterial activity. J Med Chem 51:6110–6120
Weston J (2005) Mode of action of bi- and trinuclear zinc hydrolases and their synthetic analogs. Chem Rev 105:2151–2174
Wilcox DE (1996) Binuclear metallohydrolases. Chem Rev 96:2435–2458
Xavier FR, Neves A, Casellato A, Peralta RA, Bortoluzzi AJ, Szpoganicz B, Severino PC, Terenzi H, Tomkowicz Z, Ostrovsky S, Haase W, Ozarowski A, Krzystek J, Telser J, Schenk G, Gahan LR (2009) Unsymmetrical FeIIICoII and GaIIICoII complexes as chemical hydrolases: biomimetic models for purple acid phosphatases (PAPs). Inorg Chem 48:7905–7921
Acknowledgments
J.A.L. wishes to acknowledge the National Science Foundation (USA) for financial support from grant CHE0848433 and grant CHE0820965 (MCD instrument). G.S. and N.M. acknowledge funding from the Australian Research Council (Future Fellowship) and the Science Foundation of Ireland (PIYRA Fellowship).
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Larrabee, J.A., Schenk, G., Mitić, N. et al. Use of magnetic circular dichroism to study dinuclear metallohydrolases and the corresponding biomimetics. Eur Biophys J 44, 393–415 (2015). https://doi.org/10.1007/s00249-015-1053-6
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DOI: https://doi.org/10.1007/s00249-015-1053-6