肺炎链球菌的青霉素结合蛋白2x：酶活性及与β-内酰胺类药物的相互作用
Penicillin-binding protein 2x of Streptococcus pneumoniae: enzymic activities and interactions with beta-lactams.
作者信息
Jamin M, Damblon C, Millier S, Hakenbeck R, Frère J M
机构信息
Laboratoire d'Enzymologie, Université de liège, Sart Tilman, Belgium.
出版信息
Biochem J. 1993 Jun 15;292 ( Pt 3)(Pt 3):735-41. doi: 10.1042/bj2920735.
Abstract
The high-molecular-mass penicillin-binding protein (PBP) 2x, one of the primary targets of beta-lactam antibiotics in Streptococcus pneumoniae, has been produced as a soluble form and purified in large amounts. It has been shown to catalyse hydrolysis and transfer reactions with different ester and thiolester substrates and its catalytic behaviour was often similar to that of the soluble DD-peptidase from Streptomyces R61. This provided an easy method to monitor the activity of the PBP. For the first time, a reliable kinetic study of the interaction between a lethal target and beta-lactam antibiotics has been performed. Characteristic kinetic parameters were obtained with different beta-lactam compounds. These results not only validated the mechanism established with non-essential extracellular enzymes, but will also constitute the basis for comparative studies of the low-affinity variants from penicillin-resistant strains.
摘要
高分子量青霉素结合蛋白（PBP）2x是肺炎链球菌中β-内酰胺抗生素的主要靶点之一，已被制备成可溶形式并大量纯化。已证明它能催化与不同酯和硫酯底物的水解和转移反应，其催化行为通常与来自链霉菌R61的可溶性DD-肽酶相似。这提供了一种监测PBP活性的简便方法。首次对致死靶点与β-内酰胺抗生素之间的相互作用进行了可靠的动力学研究。用不同的β-内酰胺化合物获得了特征动力学参数。这些结果不仅验证了用非必需细胞外酶建立的机制，也将构成对青霉素耐药菌株低亲和力变体进行比较研究的基础。
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本文引用的文献
1
Purification of penicillin-binding protein 3 from Streptococcus pneumoniae.
Eur J Biochem. 1982 Oct;127(2):231-6. doi: 10.1111/j.1432-1033.1982.tb06860.x.
2
A comprehensive set of sequence analysis programs for the VAX.
Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95. doi: 10.1093/nar/12.1part1.387.
3
4
Fluorescence and circular dichroism studies on the Streptomyces R61 DD-carboxypeptidase-transpeptidase. Penicillin binding by the enzyme.
Biochem J. 1973 Nov;135(3):493-505. doi: 10.1042/bj1350493.
5
Kinetics of concomitant transfer and hydrolysis reactions catalysed by the exocellular DD-carboxypeptidase-transpeptidase of streptomyces R61.
Biochem J. 1973 Nov;135(3):483-92. doi: 10.1042/bj1350483.
6
Enzymic mechanisms involving concomitant transfer and hydrolysis reactions.
Biochem J. 1973 Nov;135(3):469-81. doi: 10.1042/bj1350469.
7
Binding of beta-lactam antibiotics to the exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R39.
Biochem J. 1974 Oct;143(1):241-9. doi: 10.1042/bj1430241.
8
Interaction between beta-lactam antibiotics and exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R61.
Eur J Biochem. 1974 Dec 16;50(1):203-14. doi: 10.1111/j.1432-1033.1974.tb03889.x.
9
Sequences of the active-site peptides of three of the high-Mr penicillin-binding proteins of Escherichia coli K-12.
Proc Natl Acad Sci U S A. 1985 Apr;82(7):1999-2003. doi: 10.1073/pnas.82.7.1999.
10
Production of thiol-penicillin-binding protein 3 of Escherichia coli using a two primer method of site-directed mutagenesis.
EMBO J. 1985 Jan;4(1):231-5. doi: 10.1002/j.1460-2075.1985.tb02340.x.
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