Abstract
Antibiotic resistance to clinically employed β-lactam antibiotics currently poses a very serious threat to the clinical community. The origin of this resistance is the expression of several β-lactamases that effectively hydrolyze the amide bond in β-lactam compounds. These β-lactamases are classified into two major categories: serine β-lactamases and metallo-β-lactamases. The metalloenzymes use one or two zinc ions in their active sites to catalyze the hydrolysis of all classes of β-lactam antibiotics, including carbapenems. As there is no clinically useful inhibitor for the metallo-β-lactamases, it is important to understand the mechanism by which these enzymes catalyze the hydrolysis of antibiotics. In this regard, the development of synthetic analogues will be very useful in understanding the mechanism of action of metallo-β-lactamases. This review highlights some important contributions made by various research groups in the area of synthetic analogues of metallo-β-lactamases, with major emphasis on the role of dinuclear Zn(II) complexes in the hydrolysis of β-lactam antibiotics.
Graphical abstract
The production of metallo-β-lactamases by bacteria is becoming a serious threat to the clinical community because these enzymes are responsible for the development of antibiotic resistance to the commonly employed β-lactam antibiotics. To understand the mechanism of the hydrolysis of the β-lactam ring in the antibiotics by metallo-β-lactamases, a great deal of effort has been directed to the design and synthesis of biomimetic models for these enzymes. This review highlights some important contributions made by various research groups in the area of synthetic analogues of metallo-β-lactamases, with major emphasis on the role of dinuclear Zn(II) complexes in the hydrolysis of β-lactam antibiotics.
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References
Williams RJP (1989) In: Mills CF (ed) Zinc in human biology. Springer, Berlin, pp 15–31
Wilcox DE (1996) Chem Rev 96:2435–2458 and references therein
Lipscomb WN, Sträter N (1996) Chem Rev 96:2375–2433 and references therein
Bock WC, Katz AK, Glusker JP (1995) J Am Chem Soc 117:3754–3765
Bode W, Gomisruth FX, Huber R, Zwilling R, Stocker W (1992) Nature 358:164–167
Ippolito JA, Christianson DW (1994) Biochemistry 33:15241–15249
Hough E, Hansen LK, Birknes B, Jynge K, Hansen S, Hordvik A, Little C, Dodson E, Derewenda Z (1989) Nature 338:357–360
Klabunde T, Strater N, Frohlich R, Witzel H, Krebs B (1996) J Mol Biol 259:737–748
Christianson DW, Fierke CA (1996) Acc Chem Res 29:331–339
Christianson DW, Lipscomb WN (1989) Acc Chem Res 22:62–69
Sträter N, Lipscomb WN, Klabunde T, Krebs B (1996) Angew Chem Int Ed 35:2025–2055
Steinhagen H, Helmchem G (1996) Angew Chem Int Ed 35:2339–2342
Butler A (1998) Science 281:207–209
Weston J (2005) Chem Rev 105:2151–2174 and references therein
Bush K (1998) Clin Infect Dis 27:S48–S53 and references therein
Livermore DM (1998) J Antimicrob Chemother 41(Suppl D):25–41
Kurosaki H, Yamaguchi Y, Higashi T, Soga K, Matsueda S, Yumoto H, Misumi S, Yamagata Y, Arakawa Y, Goto M (2005) Angew Chem Int Ed 44:3861–3864
Higgins PG, Wisplinghoff H, Stefanik D, Seifert H (2004) Antimicrob Agents Chemother 48:1586–1592
Volbeda A, Lahm A, Sakiyama F, Suck D (1991) EMBO J 10:1607–1618
Crowder MW, Spencer J, Vila AJ (2006) Acc Chem Res 39:721–728 and references therein
Carfi A, Pares S, Duee E, Galleni M, Duez C, Frère J-M, Dideberg O (1995) EMBO J 14:4914–4921
Carfi A, Duée E, Galleni M, Frère J-M, Dideberg O (1998) Acta Crystallogr D 54:313–323
Fabiane SM, Sohi MK, Wan T, Payne DJ, Bateson JH, Mitchell T, Sutton B (1998) Biochemistry 37:12404–12411
Paul-Soto R, Bauer R, Frère J-M, Galleni M, Meyer-Klaucke W, Nolting H, Rossolini GM, Seny de D, Hernandez-Valladares M, Zeppezauer M, Adolph H-W (1999) J Biol Chem 274:13242–13249
Llarrul LI, Fabiane SM, Kowalski JM, Bennett B, Sutton BJ, Vila AJ (2007) J Biol Chem 282:18276–18285
Crisp J, Conners R, Garrity JD, Carenbauer AL, Crowder MW, Spencer J (2007) Biochemistry 46:10664–10674
Galleni M, Lamotte-Brasseur J, Rossolini GM, Spencer J, Dideberg O, Frère JM (2001) Antimicrob Agents Chemother 45:660–663
Concha NO, Rasmussen BA, Bush K, Herzberg O (1996) Structure 4:823–836
Paul-Soto R, Hernandez-Valladares M, Galleni M, Bauer R, Zeppezauer M, Frère J-M, Adolph H-W (1998) FEBS Lett 438:137–140
Peraro MD, Vila AJ, Carloni P, Klein ML (2007) J Am Chem Soc 129:2808–2816
Valladares MH, Felici A, Weber G, Adolph HW, Zeppezauer M, Rossolini GM, Amicosante G, Frère J-M, Galleni M (1997) Biochemistry 36:11534–11541
Garau G, Bebrone C, Anne C, Galleni M, Frère J-M, Dideberg O (2005) J Mol Biol 345:785–795
Spencer J, Read J, Sessions RB, Howell S, Blackburn GM, Gamblin SJ (2005) J Am Chem Soc 127:14439–14444
Crawford PA, Yang K-W, Sharma N, Bennett B, Crowder MW (2005) Biochemistry 44:5168–5176
Ullah JH, Walsh TR, Taylor IA, Emery DC, Verma CS, Gamblin SJ, Spencer J (1998) J Mol Biol 284:125–136
García-Saéz1 I, Mercuri PS, Papamicael C, Kahn R, Frére J-M, Galleni M, Rossolini GM, Dideberg O (2003) J Mol Biol 325:651–660
Mercuri PS, Bouillenne F, Boschi L, Lamotte-Brasseur J, Amicosante G, Devreese B, van Beeumen J, Frère J-M, Rossolini GM, Galleni M (2001) Antimicrob Agents Chemother 45:1254–1262
Morán-Barrio J, González JM, Lisa MN, Costello AL, Peraro MD, Carloni P, Bennett B, Tierney DL, Limansky AS, Viale AM, Vila AJ (2007) J Biol Chem 282:18286–18293
Koike T, Takamura M, Kimura E (1994) J Am Chem Soc 116:8443–8449
Koike T, Kimura E (2004) Encyclopedia of supramolecular chemistry. Marcel Dekker, New York, pp 178–188
Koike T, Kimura E (1991) J Am Chem Soc 113:8935–8941
Hayashi T (2004) Encyclopedia of supramolecular chemistry. Marcel Dekker, New York, pp 1631–1638
Gensmantel NP, Proctor P, Page MI (1980) J Chem Soc Perkin Trans 2 1725–1732
Montoya-Pelaez PJ, Brown RS (2002) Inorg Chem 41:309–316
Gross F, Vahrenkamp H (2005) Inorg Chem 44:4433–4440
Kaminskaia NV, Spingler B, Lippard SJ (2000) J Am Chem Soc 122:6411–6422
Kaminskaia NV, He C, Lippard SJ (2000) Inorg Chem 39:3365–3373
Bennett B, Holz RC (1997) J Am Chem Soc 119:1923–1933
Kaminskaia NV, Spingler B, Lippard SJ (2001) J Am Chem Soc 123:6555–6563
Wang Z, Fast W, Benkovic SJ (1998) J Am Chem Soc 120:10788–10789
McMannus-Munoz S, Crowder MW (1999) Biochemistry 38:1547–1553
Park H, Brothers EN, Merz KM Jr (2005) J Am Chem Soc 127:4232–4241
Garrity JD, Bennett B, Crowder MW (2005) Biochemistry 44:1078–1087
Bauer-Siebenlist B, Meyer F, Farkas E, Vidovic D, Dechert S (2005) Chem Eur J 11:4349–4360
Meyer F, Pritzkow H (2005) Eur J Inorg Chem 2346–2351
Bauer-Siebenlist B, Dechert S, Meyer F (2005) Chem Eur J 11:5343–5352 and references therein
Tamilselvi A, Nethaji M, Mugesh G (2006) Chem Eur J 12:7797–7806
Sakiyama H, Mochizuki R, Sugawara A, Sakamoto M, Nishida Y, Yamasaki M (1999) J Chem Soc Dalton Trans 997–1000
Díaz N, Suárez D, Merz KM Jr (2001) J Am Chem Soc 123:9867–9879 and references therein
Peraro MD, Vila AJ, Carloni P (2003) Inorg Chem 42:4245–4247
Orellano EG, Girardini JE, Cricco JA, Ceccarelli EA, Vila AJ (1998) Biochemistry 37:10173–10180 and references therein
Bounaga S, Laws AP, Galleni M, Page MI (1998) Biochem J 331:61–68
Rasia RM, Vila AJ (2002) Biochemistry 41:1853–1860
Park H-S, Nam S-H, Lee JK, Yoon C, Mannervik B, Benkovic SJ, Kim H-S (2006) Science 311:535–538
Acknowledgments
This study was supported by the Department of Science and Technology (DST), New Delhi, India. G.M. acknowledges the DST for the award of Ramanna Fellowship and A.T. thanks the University Grants Commission (UGC), New Delhi, for a research fellowship.
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Tamilselvi, A., Mugesh, G. Zinc and antibiotic resistance: metallo-β-lactamases and their synthetic analogues. J Biol Inorg Chem 13, 1039–1053 (2008). https://doi.org/10.1007/s00775-008-0407-2
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DOI: https://doi.org/10.1007/s00775-008-0407-2