4MUK

Crystal structure of pantothenate synthetase in complex with 2-(5-methoxy-2-(4-(trifluoromethyl)benzylsulfonylcarbamoyl)-1H-indol-1-yl)acetic acid

4MUK の概要

• エントリーDOI: 10.2210/pdb4muk/pdb
• 関連するPDBエントリー: 4MQ6 4MUE 4MUF 4MUG 4MUH 4MUI 4MUL 4MUN
• 分子名称: Pantothenate synthetase, [5-methoxy-2-({[4-(trifluoromethyl)benzyl]sulfonyl}carbamoyl)-1H-indol-1-yl]acetic acid, ETHANOL, ... (5 entities in total)
• 機能のキーワード: alpha beta 3-layer(aba) sandwich rossmann fold, pantoate-ligase, atp binding, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64481.72

構造登録者

Silvestre, H.L.,Blundell, T.L. (登録日: 2013-09-22, 公開日: 2014-08-27, 最終更新日: 2023-09-20)

主引用文献

Hung, A.W.,Silvestre, H.L.,Wen, S.,George, G.P.,Boland, J.,Blundell, T.L.,Ciulli, A.,Abell, C.
Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis.
Chemmedchem, 11:38-42, 2016

PubMed Abstract: Ligand efficiency has proven to be a valuable concept for optimization of leads in the early stages of drug design. Taking this one step further, group efficiency (GE) evaluates the binding efficiency of each appendage of a molecule, further fine-tuning the drug design process. Here, GE analysis is used to systematically improve the potency of inhibitors of Mycobacterium tuberculosis pantothenate synthetase, an important target in tuberculosis therapy. Binding efficiencies were found to be distributed unevenly within a lead molecule derived using a fragment-based approach. Substitution of the less efficient parts of the molecule allowed systematic development of more potent compounds. This method of dissecting and analyzing different groups within a molecule offers a rational and general way of carrying out lead optimization, with potential broad application within drug discovery.

PubMed: 26486566
DOI: 10.1002/cmdc.201500414

実験手法

X-RAY DIFFRACTION (1.9 Å)