2AM2

sp protein ligand 2

2AM2 の概要

• エントリーDOI: 10.2210/pdb2am2/pdb
• 関連するPDBエントリー: 2AM1
• 分子名称: UDP-N-acetylmuramoylalanine-D-glutamyl-lysine-D-alanyl-D-alanine ligase, MurF protein, 2-CHLORO-N-(3-CYANO-5,6-DIHYDRO-4H-CYCLOPENTA[B]THIOPHEN-2-YL)-5-DIETHYLSULFAMOYL-BENZAMIDE (3 entities in total)
• 機能のキーワード: ligase
• 由来する生物種: Streptococcus pneumoniae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51184.57

構造登録者

Longenecker, K.L.,Stamper, G.F.,Hajduk, P.J.,Fry, E.H.,Jakob, C.G.,Harlan, J.E.,Edalji, R.,Bartley, D.M.,Walter, K.A.,Solomon, L.R. (登録日: 2005-08-08, 公開日: 2006-01-24, 最終更新日: 2024-10-30)

主引用文献

Longenecker, K.L.,Stamper, G.F.,Hajduk, P.J.,Fry, E.H.,Jakob, C.G.,Harlan, J.E.,Edalji, R.,Bartley, D.M.,Walter, K.A.,Solomon, L.R.,Holzman, T.F.,Gu, Y.G.,Lerner, C.G.,Beutel, B.A.,Stoll, V.S.
Structure of MurF from Streptococcus pneumoniae co-crystallized with a small molecule inhibitor exhibits interdomain closure
Protein Sci., 14:3039-3047, 2005

PubMed Abstract: In a broad genomics analysis to find novel protein targets for antibiotic discovery, MurF was identified as an essential gene product for Streptococcus pneumonia that catalyzes a critical reaction in the biosynthesis of the peptidoglycan in the formation of the cell wall. Lacking close relatives in mammalian biology, MurF presents attractive characteristics as a potential drug target. Initial screening of the Abbott small-molecule compound collection identified several compounds for further validation as pharmaceutical leads. Here we report the integrated efforts of NMR and X-ray crystallography, which reveal the multidomain structure of a MurF-inhibitor complex in a compact conformation that differs dramatically from related structures. The lead molecule is bound in the substrate-binding region and induces domain closure, suggestive of the domain arrangement for the as yet unobserved transition state conformation for MurF enzymes. The results form a basis for directed optimization of the compound lead by structure-based design to explore the suitability of MurF as a pharmaceutical target.

PubMed: 16322581
DOI: 10.1110/ps.051604805

実験手法

X-RAY DIFFRACTION (2.8 Å)