1K25

PBP2x from a Highly Penicillin-resistant Streptococcus pneumoniae Clinical Isolate

1K25 の概要

• エントリーDOI: 10.2210/pdb1k25/pdb
• 関連するPDBエントリー: 1QME 1QMF
• 分子名称: low-affinity PENICILLIN-BINDING PROTEIN 2X (2 entities in total)
• 機能のキーワード: antibiotic resistance, clinical mutant, low-affinity penicillin-binding, membrane protein
• 由来する生物種: Streptococcus pneumoniae
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 301037.72

構造登録者

Dessen, A.,Mouz, N.,Hopkins, J.,Dideberg, O. (登録日: 2001-09-26, 公開日: 2001-10-31, 最終更新日: 2024-02-07)

主引用文献

Dessen, A.,Mouz, N.,Gordon, E.,Hopkins, J.,Dideberg, O.
Crystal structure of PBP2x from a highly penicillin-resistant Streptococcus pneumoniae clinical isolate: a mosaic framework containing 83 mutations.
J.Biol.Chem., 276:45106-45112, 2001

PubMed Abstract: Penicillin-binding proteins (PBPs) are the main targets for beta-lactam antibiotics, such as penicillins and cephalosporins, in a wide range of bacterial species. In some Gram-positive strains, the surge of resistance to treatment with beta-lactams is primarily the result of the proliferation of mosaic PBP-encoding genes, which encode novel proteins by recombination. PBP2x is a primary resistance determinant in Streptococcus pneumoniae, and its modification is an essential step in the development of high level beta-lactam resistance. To understand such a resistance mechanism at an atomic level, we have solved the x-ray crystal structure of PBP2x from a highly penicillin-resistant clinical isolate of S. pneumoniae, Sp328, which harbors 83 mutations in the soluble region. In the proximity of the Sp328 PBP2x* active site, the Thr(338) --> Ala mutation weakens the local hydrogen bonding network, thus abrogating the stabilization of a crucial buried water molecule. In addition, the Ser(389) --> Leu and Asn(514) --> His mutations produce a destabilizing effect that generates an "open" active site. It has been suggested that peptidoglycan substrates for beta-lactam-resistant PBPs contain a large amount of abnormal, branched peptides, whereas sensitive strains tend to catalyze cross-linking of linear forms. Thus, in vivo, an "open" active site could facilitate the recognition of distinct, branched physiological substrates.

PubMed: 11553637
DOI: 10.1074/jbc.M107608200

実験手法

X-RAY DIFFRACTION (3.2 Å)