1KVM

X-ray Crystal Structure of AmpC WT beta-Lactamase in Complex with Covalently Bound Cephalothin

1KVM の概要

• エントリーDOI: 10.2210/pdb1kvm/pdb
• 関連するPDBエントリー: 1KE4 1KVL 2BLS
• 分子名称: beta-lactamase, PHOSPHATE ION, 5-METHYLENE-2-[2-OXO-1-(2-THIOPHEN-2-YL-ACETYLAMINO)-ETHYL]-5,6-DIHYDRO-2H-[1,3]THIAZINE-4-CARBOXYLIC ACID, ... (4 entities in total)
• 機能のキーワード: amide hydrolase, beta-lactamase, cephalothin, acyl-enzyme complex, hydrolase
• 由来する生物種: Escherichia coli
• 細胞内の位置: Periplasm: P00811
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79609.22

構造登録者

Beadle, B.M.,Trehan, I.,Focia, P.J.,Shoichet, B.K. (登録日: 2002-01-27, 公開日: 2002-03-13, 最終更新日: 2024-10-09)

主引用文献

Beadle, B.M.,Trehan, I.,Focia, P.J.,Shoichet, B.K.
Structural milestones in the reaction pathway of an amide hydrolase: substrate, acyl, and product complexes of cephalothin with AmpC beta-lactamase.
Structure, 10:413-424, 2002

PubMed Abstract: Beta-lactamases hydrolyze beta-lactam antibiotics and are the leading cause of bacterial resistance to these drugs. Although beta-lactamases have been extensively studied, structures of the substrate-enzyme and product-enzyme complexes have proven elusive. Here, the structure of a mutant AmpC in complex with the beta-lactam cephalothin in its substrate and product forms was determined by X-ray crystallography to 1.53 A resolution. The acyl-enzyme intermediate between AmpC and cephalothin was determined to 2.06 A resolution. The ligand undergoes a dramatic conformational change as the reaction progresses, with the characteristic six-membered dihydrothiazine ring of cephalothin rotating by 109 degrees. These structures correspond to all three intermediates along the reaction path and provide insight into substrate recognition, catalysis, and product expulsion.

PubMed: 12005439
DOI: 10.1016/S0969-2126(02)00725-6

実験手法

X-RAY DIFFRACTION (2.06 Å)