3UPN

Structure of penicillin-binding protein A from M. tuberculosis: imipenem acyl-enzyme complex

3UPN の概要

• エントリーDOI: 10.2210/pdb3upn/pdb
• 関連するPDBエントリー: 3LO7 3UN7 3UPO 3UPP
• 分子名称: Penicillin-binding protein A, (5R)-5-[(1S,2R)-1-formyl-2-hydroxypropyl]-3-[(2-{[(E)-iminomethyl]amino}ethyl)sulfanyl]-4,5-dihydro-1H-pyrrole-2-carbox ylic acid (3 entities in total)
• 機能のキーワード: transpeptidase, peptidoglycan, beta-lactam, penicillin-binding protein-antibiotic complex, penicillin-binding protein/antibiotic
• 由来する生物種: Mycobacterium tuberculosis
• 細胞内の位置: Cell membrane; Single-pass type II membrane protein (Probable): P71586
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97531.71

構造登録者

Davies, C.,Fedorovich, A. (登録日: 2011-11-18, 公開日: 2012-10-24, 最終更新日: 2023-09-13)

主引用文献

Fedarovich, A.,Nicholas, R.A.,Davies, C.
The role of the beta5-alpha11 loop in the active-site dynamics of acylated penicillin-binding protein A from Mycobacterium tuberculosis
J.Mol.Biol., 418:316-330, 2012

PubMed Abstract: Penicillin-binding protein A (PBPA) is a class B penicillin-binding protein that is important for cell division in Mycobacterium tuberculosis. We have determined a second crystal structure of PBPA in apo form and compared it with an earlier structure of apoenzyme. Significant structural differences in the active site region are apparent, including increased ordering of a β-hairpin loop and a shift of the SxN active site motif such that it now occupies a position that appears catalytically competent. Using two assays, including one that uses the intrinsic fluorescence of a tryptophan residue, we have also measured the second-order acylation rate constants for the antibiotics imipenem, penicillin G, and ceftriaxone. Of these, imipenem, which has demonstrable anti-tubercular activity, shows the highest acylation efficiency. Crystal structures of PBPA in complex with the same antibiotics were also determined, and all show conformational differences in the β5-α11 loop near the active site, but these differ for each β-lactam and also for each of the two molecules in the crystallographic asymmetric unit. Overall, these data reveal the β5-α11 loop of PBPA as a flexible region that appears important for acylation and provide further evidence that penicillin-binding proteins in apo form can occupy different conformational states.

PubMed: 22365933
DOI: 10.1016/j.jmb.2012.02.021

実験手法

X-RAY DIFFRACTION (2.2 Å)