8BV4

Structure of BlaC from Mycobacterium tuberculosis in complex with vaborbactam

8BV4 の概要

• エントリーDOI: 10.2210/pdb8bv4/pdb
• 分子名称: Beta-lactamase, Vaborbactam, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29600.15

構造登録者

Chikunova, A.,Bruenle, S.,Ubbink, M. (登録日: 2022-12-01, 公開日: 2023-07-05, 最終更新日: 2024-02-07)

主引用文献

van Alen, I.,Chikunova, A.,van Zanten, D.B.,de Block, A.A.,Timmer, M.,Brunle, S.,Ubbink, M.
Asp179 in the class A beta-lactamase from Mycobacterium tuberculosis is a conserved yet not essential residue due to epistasis.
Febs J., 290:4933-4949, 2023

PubMed Abstract: Conserved residues are often considered essential for function, and substitutions in such residues are expected to have a negative influence on the properties of a protein. However, mutations in a few highly conserved residues of the β-lactamase from Mycobacterium tuberculosis, BlaC, were shown to have no or only limited negative effect on the enzyme. One such mutant, D179N, even conveyed increased ceftazidime resistance upon bacterial cells, while displaying good activity against penicillins. The crystal structures of BlaC D179N in resting state and in complex with sulbactam reveal subtle structural changes in the Ω-loop as compared to the structure of wild-type BlaC. Introducing this mutation in four other β-lactamases, CTX-M-14, KPC-2, NMC-A and TEM-1, resulted in decreased antibiotic resistance for penicillins and meropenem. The results demonstrate that the Asp in position 179 is generally essential for class A β-lactamases but not for BlaC, which can be explained by the importance of the interaction with the side chain of Arg164 that is absent in BlaC. It is concluded that Asp179 though conserved is not essential in BlaC, as a consequence of epistasis.

PubMed: 37335937
DOI: 10.1111/febs.16892

実験手法

X-RAY DIFFRACTION (1.95 Å)