Comparative Characterization of CTX-M-64 and CTX-M-14 Provides Insights into the Structure and Catalytic Activity of the CTX-M Class of Enzymes

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

7 Scopus Citations
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Author(s)

  • Dandan He
  • Jiachi Chiou
  • Zhenling Zeng
  • Edward Wai-Chi Chan
  • Jian-Hua Liu

Detail(s)

Original languageEnglish
Pages (from-to)6084-6090
Journal / PublicationAntimicrobial Agents and Chemotherapy
Volume60
Issue number10
Online published23 Sep 2016
Publication statusPublished - Oct 2016
Externally publishedYes

Abstract

Clinical isolates producing hybrid CTX-M β-lactamases, presumably due to recombination between the blaCTX-M-15 and blaCTX-M-14 elements, have emerged in recent years. Among the hybrid enzymes, CTX-M-64 and CTX-M-14 display the most significant difference in catalytic activity. This study aims to investigate the mechanisms underlying such differential enzymatic activities in order to provide insight into the structure/function relationship of this class of enzymes. Sequence alignment analysis showed that the major differences between the amino acid composition of CTX-M-64 and CTX-M-14 lie at both the N and C termini of the enzymes. Single or multiple amino acid substitutions introduced into CTX-M-64 and CTX-M-14 were found to produce only minor effects on hydrolytic functions; such a finding is consistent with the notion that the discrepancy between the functional activities of the two enzymes is not the result of only a few amino acid changes but is attributable to interactions between a unique set of amino acid residues in each enzyme. This theory is supported by the results of the thermal stability assay, which confirmed that CTX-M-64 is significantly more stable than CTX-M-14. Our data confirmed that, in addition to the important residues located in the active site, residues distal to the active site also contribute to the catalytic activity of the enzyme through stabilizing its structural integrity.

Citation Format(s)

Comparative Characterization of CTX-M-64 and CTX-M-14 Provides Insights into the Structure and Catalytic Activity of the CTX-M Class of Enzymes. / He, Dandan; Chiou, Jiachi; Zeng, Zhenling; Chan, Edward Wai-Chi; Liu, Jian-Hua; Chen, Sheng.

In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 10, 10.2016, p. 6084-6090.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal