1FR1

REFINED CRYSTAL STRUCTURE OF BETA-LACTAMASE FROM CITROBACTER FREUNDII INDICATES A MECHANISM FOR BETA-LACTAM HYDROLYSIS

1FR1 の概要

• エントリーDOI: 10.2210/pdb1fr1/pdb
• 関連するPDBエントリー: 1FR6
• 分子名称: BETA-LACTAMASE (2 entities in total)
• 機能のキーワード: hydrolase, antibiotic resistance, class c beta-lactamase
• 由来する生物種: Citrobacter freundii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79510.50

構造登録者

Oefner, C.,D'Arcy, A.,Daly, J.J.,Winkler, F.K. (登録日: 2000-09-07, 公開日: 2001-01-17, 最終更新日: 2024-02-07)

主引用文献

Oefner, C.,D'Arcy, A.,Daly, J.J.,Gubernator, K.,Charnas, R.L.,Heinze, I.,Hubschwerlen, C.,Winkler, F.K.
Refined crystal structure of beta-lactamase from Citrobacter freundii indicates a mechanism for beta-lactam hydrolysis.
Nature, 343:284-288, 1990

PubMed Abstract: Beta-Lactamases (EC 3.5.2.6, 'penicillinases') are a family of enzymes that protect bacteria against the lethal effects of cell-wall synthesis of penicillins, cephalosporins and related antibiotic agents, by hydrolysing the beta-lactam antibiotics to biologically inactive compounds. Their production can, therefore, greatly contribute to the clinical problem of antibiotic resistance. Three classes of beta-lactamases--A, B and C--have been identified on the basis of their amino-acid sequence; class B beta-lactamases are metalloenzymes, and are clearly distinct from members of class A and C beta-lactamases, which both contain an active-site serine residue involved in the formation of an acyl enzyme with beta-lactam substrates during catalysis. It has been predicted that class C beta-lactamases share common structural features with D,D-carboxypeptidases and class A beta-lactamases, and further, suggested that class A and class C beta-lactamases have the same evolutionary origin as other beta-lactam target enzymes. We report here the refined three-dimensional structure of the class C beta-lactamase from Citrobacter freundii at 2.0-A resolution and confirm the predicted structural similarity. The refined structure of the acyl-enzyme formed with the monobactam inhibitor aztreonam at 2.5-A resolution defines the enzyme's active site and, along with molecular modelling, indicates a mechanism for beta-lactam hydrolysis. This leads to the hypothesis that Tyr 150 functions as a general base during catalysis.

PubMed: 2300174
DOI: 10.1038/343284a0

実験手法

X-RAY DIFFRACTION (2 Å)