7LNO

Structure of apo-CDD-1 beta-lactamase in imidazole and MPD

7LNO の概要

• エントリーDOI: 10.2210/pdb7lno/pdb
• 分子名称: Beta-lactamase, SULFATE ION, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• 機能のキーワード: beta-lactamase, antibiotic resistance, hydrolase
• 由来する生物種: Clostridioides difficile
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36833.67

構造登録者

Smith, C.A.,Vakulenko, S.B.,Stewart, N.K. (登録日: 2021-02-08, 公開日: 2021-05-12, 最終更新日: 2023-11-15)

主引用文献

Stewart, N.K.,Toth, M.,Stasyuk, A.,Vakulenko, S.B.,Smith, C.A.
In Crystallo Time-Resolved Interaction of the Clostridioides difficile CDD-1 enzyme with Avibactam Provides New Insights into the Catalytic Mechanism of Class D beta-lactamases.
Acs Infect Dis., 7:1765-1776, 2021

PubMed Abstract: Class D β-lactamases have risen to notoriety due to their wide spread in bacterial pathogens, propensity to inactivate clinically important β-lactam antibiotics, and ability to withstand inhibition by the majority of classical β-lactamase inhibitors. Understanding the catalytic mechanism of these enzymes is thus vitally important for the development of novel antibiotics and inhibitors active against infections caused by antibiotic-resistant bacteria. Here we report an time-resolved study of the interaction of the class D β-lactamase CDD-1 from with the diazobicyclooctane inhibitor, avibactam. We show that the catalytic carboxylated lysine, a residue that is essential for both acylation and deacylation of β-lactams, is sequestered within an internal sealed pocket of the enzyme. Time-resolved snapshots generated in this study allowed us to observe decarboxylation of the lysine and movement of CO and water molecules through a transient channel formed between the lysine pocket and the substrate binding site facilitated by rotation of the side chain of a conserved leucine residue. These studies provide novel insights on avibactam binding to CDD-1 and into the catalytic mechanism of class D β-lactamases in general.

PubMed: 33908775
DOI: 10.1021/acsinfecdis.1c00094

実験手法

X-RAY DIFFRACTION (1.58 Å)