1CEF

CEFOTAXIME COMPLEXED WITH THE STREPTOMYCES R61 DD-PEPTIDASE

1CEF の概要

• エントリーDOI: 10.2210/pdb1cef/pdb
• 分子名称: D-ALANYL-D-ALANINE CARBOXYPEPTIDASE TRANSPEPTIDASE, CEFOTAXIME, C3' cleaved, open, bound form (3 entities in total)
• 機能のキーワード: d-amino acid peptidase, penicillin target, hydrolase-transpeptidase
• 由来する生物種: Streptomyces sp.
• 細胞内の位置: Secreted: P15555
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37820.00

構造登録者

Knox, J.R.,Kuzin, A.P. (登録日: 1995-01-12, 公開日: 1996-10-14, 最終更新日: 2024-10-30)

主引用文献

Kuzin, A.P.,Liu, H.,Kelly, J.A.,Knox, J.R.
Binding of cephalothin and cefotaxime to D-ala-D-ala-peptidase reveals a functional basis of a natural mutation in a low-affinity penicillin-binding protein and in extended-spectrum beta-lactamases.
Biochemistry, 34:9532-9540, 1995

PubMed Abstract: Two clinically-important beta-lactam antibiotics, cephalothin and cefotaxime, have been observed by X-ray crystallography bound to the reactive Ser62 of the D-alanyl-D-alanine carboxypeptidase/transpeptidase of Streptomyces sp. R61. Refinement of the two crystal structures produced R factors for 3 sigma (F) data of 0.166 (to 1.8 A) and 0.170 (to 2.0 A) for the cephalothin and cefotaxime complexes, respectively. In each complex, a water molecule is within 3.1 and 3.6 A of the acylated beta-lactam carbonyl carbon atom, but is poorly activated by active site residues for nucleophilic attack and deacylation. This apparent lack of good stereochemistry for facile hydrolysis is in accord with the long half-lives of cephalosporin intermediates in solution (20-40 h) and the efficacy of these beta-lactams as inhibitors of bacterial cell wall synthesis. Different hydrogen binding patterns of the two cephalosporins to Thr301 are consistent with the low cefotaxime affinity of an altered penicillin-binding protein, PBP-2x, reported in cefotaxime-resistant strains of Streptococcus pneumoniae, and with the ability of mutant class A beta-lactamases to hydrolyze third-generation cephalosporins.

PubMed: 7626623
DOI: 10.1021/bi00029a030

実験手法

X-RAY DIFFRACTION (2.04 Å)