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. 1994 Sep 15;302(Pt 3):851–856. doi: 10.1042/bj3020851

Relative specificities of a series of beta-lactam-recognizing enzymes towards the side-chains of penicillins and of acyclic thioldepsipeptides.

Y Xu 1, G Soto 1, H Adachi 1, M P van der Linden 1, W Keck 1, R F Pratt 1
PMCID: PMC1137308  PMID: 7945212

Abstract

In an attempt to understand more of the subtle differences between bacterial beta-lactamases and DD-peptidases, comparisons have been made between the specificities of these enzymes towards the phenylacetyl side chain, generally thought to be favoured by beta-lactamases, and the NN'-diacetyl-L-lysyl side chain, widely employed in low-molecular-mass substrates of DD-peptidases. These comparisons were carried out with both a penicillin and an acyclic thioldepsipeptide reaction nucleus and employing a range of both beta-lactamases and DD-peptidases. Rather contrary to general expectations, a general preference for reaction of both groups of enzymes with penicillins rather than thioldepsipeptides was observed and for the phenylacetyl rather than the NN'-diacetyl-L-lysyl side chain. Quantitative comparisons suggested that the side chains of penicillins may be bound in relatively similar sites in all of the enzymes whereas the side chains of thioldepsipeptides are more heterogeneously bound, both with respect to each other and to the comparable side chains of penicillins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adachi H., Ohta T., Matsuzawa H. A water-soluble form of penicillin-binding protein 2 of Escherichia coli constructed by site-directed mutagenesis. FEBS Lett. 1987 Dec 21;226(1):150–154. doi: 10.1016/0014-5793(87)80569-0. [DOI] [PubMed] [Google Scholar]
  2. Adam M., Damblon C., Plaitin B., Christiaens L., Frère J. M. Chromogenic depsipeptide substrates for beta-lactamases and penicillin-sensitive DD-peptidases. Biochem J. 1990 Sep 1;270(2):525–529. doi: 10.1042/bj2700525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anderson E. G., Pratt R. F. Pre-steady state beta-lactamase kinetics. The trapping of a covalent intermediate and the interpretation of pH rate profiles. J Biol Chem. 1983 Nov 10;258(21):13120–13126. [PubMed] [Google Scholar]
  4. Berg O. G. Orientation constraints in diffusion-limited macromolecular association. The role of surface diffusion as a rate-enhancing mechanism. Biophys J. 1985 Jan;47(1):1–14. doi: 10.1016/S0006-3495(85)83870-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bicknell R., Waley S. G. Cryoenzymology of Bacillus cereus beta-lactamase II. Biochemistry. 1985 Nov 19;24(24):6876–6887. doi: 10.1021/bi00345a021. [DOI] [PubMed] [Google Scholar]
  6. Brain E. G., McMillan I., Nayler J. H., Southgate R., Tolliday P. The chemistry of penicillanic acids. Part III. A route to 1,2-secopenicillins. J Chem Soc Perkin 1. 1975;(6):562–567. [PubMed] [Google Scholar]
  7. Brocklehurst K., Little G. Reactions of papain and of low-molecular-weight thiols with some aromatic disulphides. 2,2'-Dipyridyl disulphide as a convenient active-site titrant for papain even in the presence of other thiols. Biochem J. 1973 May;133(1):67–80. doi: 10.1042/bj1330067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Christensen H., Martin M. T., Waley S. G. Beta-lactamases as fully efficient enzymes. Determination of all the rate constants in the acyl-enzyme mechanism. Biochem J. 1990 Mar 15;266(3):853–861. [PMC free article] [PubMed] [Google Scholar]
  9. Frère J. M., Joris B., Varetto L., Crine M. Structure-activity relationships in the beta-lactam family: an impossible dream. Biochem Pharmacol. 1988 Jan 1;37(1):125–132. doi: 10.1016/0006-2952(88)90764-2. [DOI] [PubMed] [Google Scholar]
  10. Galleni M., Amicosante G., Frère J. M. A survey of the kinetic parameters of class C beta-lactamases. Cephalosporins and other beta-lactam compounds. Biochem J. 1988 Oct 1;255(1):123–129. doi: 10.1042/bj2550123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Galleni M., Frère J. M. A survey of the kinetic parameters of class C beta-lactamases. Penicillins. Biochem J. 1988 Oct 1;255(1):119–122. doi: 10.1042/bj2550119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ghuysen J. M., Frère J. M., Leyh-Bouille M., Coyette J., Dusart J., Nguyen-Distèche M. Use of model enzymes in the determination of the mode of action of penicillins and delta 3-cephalosporins. Annu Rev Biochem. 1979;48:73–101. doi: 10.1146/annurev.bi.48.070179.000445. [DOI] [PubMed] [Google Scholar]
  13. Ghuysen J. M. Serine beta-lactamases and penicillin-binding proteins. Annu Rev Microbiol. 1991;45:37–67. doi: 10.1146/annurev.mi.45.100191.000345. [DOI] [PubMed] [Google Scholar]
  14. Govardhan C. P., Pratt R. F. Kinetics and mechanism of the serine beta-lactamase catalyzed hydrolysis of depsipeptides. Biochemistry. 1987 Jun 16;26(12):3385–3395. doi: 10.1021/bi00386a021. [DOI] [PubMed] [Google Scholar]
  15. Hardy L. W., Kirsch J. F. Diffusion-limited component of reactions catalyzed by Bacillus cereus beta-lactamase I. Biochemistry. 1984 Mar;23(6):1275–1282. doi: 10.1021/bi00301a040. [DOI] [PubMed] [Google Scholar]
  16. Herzberg O., Moult J. Bacterial resistance to beta-lactam antibiotics: crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.5 A resolution. Science. 1987 May 8;236(4802):694–701. doi: 10.1126/science.3107125. [DOI] [PubMed] [Google Scholar]
  17. Kelly J. A., Dideberg O., Charlier P., Wery J. P., Libert M., Moews P. C., Knox J. R., Duez C., Fraipont C., Joris B. On the origin of bacterial resistance to penicillin: comparison of a beta-lactamase and a penicillin target. Science. 1986 Mar 21;231(4744):1429–1431. doi: 10.1126/science.3082007. [DOI] [PubMed] [Google Scholar]
  18. Kelly J. A., Knox J. R., Zhao H., Frère J. M., Ghaysen J. M. Crystallographic mapping of beta-lactams bound to a D-alanyl-D-alanine peptidase target enzyme. J Mol Biol. 1989 Sep 20;209(2):281–295. doi: 10.1016/0022-2836(89)90277-5. [DOI] [PubMed] [Google Scholar]
  19. Lamotte-Brasseur J., Dive G., Dideberg O., Charlier P., Frère J. M., Ghuysen J. M. Mechanism of acyl transfer by the class A serine beta-lactamase of Streptomyces albus G. Biochem J. 1991 Oct 1;279(Pt 1):213–221. doi: 10.1042/bj2790213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lienhard G. E., Jencks W. P. Thiol addition to the carbonyl group. Equilibria and kinetics. J Am Chem Soc. 1966 Sep 5;88(17):3982–3994. doi: 10.1021/ja00969a017. [DOI] [PubMed] [Google Scholar]
  21. Lobkovsky E., Moews P. C., Liu H., Zhao H., Frere J. M., Knox J. R. Evolution of an enzyme activity: crystallographic structure at 2-A resolution of cephalosporinase from the ampC gene of Enterobacter cloacae P99 and comparison with a class A penicillinase. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11257–11261. doi: 10.1073/pnas.90.23.11257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Matagne A., Misselyn-Bauduin A. M., Joris B., Erpicum T., Granier B., Frère J. M. The diversity of the catalytic properties of class A beta-lactamases. Biochem J. 1990 Jan 1;265(1):131–146. doi: 10.1042/bj2650131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Moews P. C., Knox J. R., Dideberg O., Charlier P., Frère J. M. Beta-lactamase of Bacillus licheniformis 749/C at 2 A resolution. Proteins. 1990;7(2):156–171. doi: 10.1002/prot.340070205. [DOI] [PubMed] [Google Scholar]
  24. Murphy B. P., Pratt R. F. N-(phenylacetyl)glycyl-D-aziridine-2-carboxylate, an acyclic amide substrate of beta-lactamases: importance of the shape of the substrate in beta-lactamase evolution. Biochemistry. 1991 Apr 16;30(15):3640–3649. doi: 10.1021/bi00229a008. [DOI] [PubMed] [Google Scholar]
  25. Oefner C., D'Arcy A., Daly J. J., Gubernator K., Charnas R. L., Heinze I., Hubschwerlen C., Winkler F. K. Refined crystal structure of beta-lactamase from Citrobacter freundii indicates a mechanism for beta-lactam hydrolysis. Nature. 1990 Jan 18;343(6255):284–288. doi: 10.1038/343284a0. [DOI] [PubMed] [Google Scholar]
  26. Pazhanisamy S., Pratt R. F. Beta-lactamase-catalyzed aminolysis of depsipeptides: peptide inhibition and a new kinetic mechanism. Biochemistry. 1989 Aug 22;28(17):6875–6882. doi: 10.1021/bi00443a015. [DOI] [PubMed] [Google Scholar]
  27. Pratt R. F., Govardhan C. P. beta-Lactamase-catalyzed hydrolysis of acyclic depsipeptides and acyl transfer to specific amino acid acceptors. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1302–1306. doi: 10.1073/pnas.81.5.1302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Strynadka N. C., Adachi H., Jensen S. E., Johns K., Sielecki A., Betzel C., Sutoh K., James M. N. Molecular structure of the acyl-enzyme intermediate in beta-lactam hydrolysis at 1.7 A resolution. Nature. 1992 Oct 22;359(6397):700–705. doi: 10.1038/359700a0. [DOI] [PubMed] [Google Scholar]
  29. Tipper D. J., Strominger J. L. Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc Natl Acad Sci U S A. 1965 Oct;54(4):1133–1141. doi: 10.1073/pnas.54.4.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tomasz A. The mechanism of the irreversible antimicrobial effects of penicillins: how the beta-lactam antibiotics kill and lyse bacteria. Annu Rev Microbiol. 1979;33:113–137. doi: 10.1146/annurev.mi.33.100179.000553. [DOI] [PubMed] [Google Scholar]
  31. WILKINSON G. N. Statistical estimations in enzyme kinetics. Biochem J. 1961 Aug;80:324–332. doi: 10.1042/bj0800324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Waley S. G. A spectrophotometric assay of beta-lactamase action on penicillins. Biochem J. 1974 Jun;139(3):789–790. doi: 10.1042/bj1390789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. van der Linden M. P., Mottl H., Keck W. Cytoplasmic high-level expression of a soluble, enzymatically active form of the Escherichia coli penicillin-binding protein 5 and purification by dye chromatography. Eur J Biochem. 1992 Feb 15;204(1):197–202. doi: 10.1111/j.1432-1033.1992.tb16624.x. [DOI] [PubMed] [Google Scholar]

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