3ZQD

B. subtilis L,D-transpeptidase

3ZQD の概要

• エントリーDOI: 10.2210/pdb3zqd/pdb
• 関連するPDBエントリー: 1Y7M
• NMR情報: BMRB: 17701
• 分子名称: L, D-TRANSPEPTIDASE YKUD (1 entity in total)
• 機能のキーワード: transferase, peptidoglycan, antibiotic resistance, cysteine protease
• 由来する生物種: BACILLUS SUBTILIS SUBSP. SUBTILIS
• 細胞内の位置: Spore wall : O34816
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18960.73

構造登録者

Lecoq, L.,Simorre, J.-P.,Bougault, C.,Arthur, M.,Hugonnet, J.-E.,Veckerle, C.,Pessey, O. (登録日: 2011-06-09, 公開日: 2012-05-23, 最終更新日: 2024-06-19)

主引用文献

Lecoq, L.,Bougault, C.,Hugonnet, J.,Veckerle, C.,Pessey, O.,Arthur, M.,Simorre, J.
Dynamics Induced by Beta-Lactam Antibiotics in the Active Site of Bacillus subtilis L,D-Transpeptidase.
Structure, 20:850-861, 2012

PubMed Abstract: β-lactams inhibit peptidoglycan polymerization by acting as suicide substrates of essential d,d-transpeptidases. Bypass of these enzymes by unrelated l,d-transpeptidases results in β-lactam resistance, although carbapenems remain unexpectedly active. To gain insight into carbapenem specificity of l,d-transpeptidases (Ldts), we solved the nuclear magnetic resonance (NMR) structures of apo and imipenem-acylated Bacillus subtilis Ldt and show that the cysteine nucleophile is present as a neutral imidazole-sulfhydryl pair in the substrate-free enzyme. NMR relaxation dispersion does not reveal any preexisting conformational exchange in the apoenzyme, and change in flexibility is not observed upon noncovalent binding of β-lactams (K(D) > 37.5 mM). In contrast, covalent modification of active cysteine by both carbapenems and 2-nitro-5-thiobenzoate induces backbone flexibility that does not result from disruption of the imidazole-sulfhydryl proton interaction or steric hindrance. The chemical step of the reaction determines enzyme specificity since no differences in drug affinity were observed.

PubMed: 22579252
DOI: 10.1016/J.STR.2012.03.015

実験手法

SOLUTION NMR