4KIJ

Design and structural analysis of aromatic inhibitors of type II dehydroquinase dehydratase from Mycobacterium tuberculosis - compound 35c [3,4-dihydroxy-5-(3-nitrophenoxy)benzoic acid]

4KIJ の概要

• エントリーDOI: 10.2210/pdb4kij/pdb
• 関連するPDBエントリー: 4KI7 4KIM 4KIU 4KIW 4KL9 4KLX 4KM0 4KM2
• 分子名称: 3-dehydroquinate dehydratase, CHLORIDE ION, 3,4-dihydroxy-5-(3-nitrophenoxy)benzoic acid, ... (4 entities in total)
• 機能のキーワード: dehydratase, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16925.48

構造登録者

Dias, M.V.B.,Howard, N.G.,Blundell, T.L.,Abell, C. (登録日: 2013-05-02, 公開日: 2014-05-14, 最終更新日: 2024-02-28)

主引用文献

Howard, N.I.,Dias, M.V.,Peyrot, F.,Chen, L.,Schmidt, M.F.,Blundell, T.L.,Abell, C.
Design and Structural Analysis of Aromatic Inhibitors of Type II Dehydroquinase from Mycobacterium tuberculosis.
Chemmedchem, 10:116-133, 2015

PubMed Abstract: 3-Dehydroquinase, the third enzyme in the shikimate pathway, is a potential target for drugs against tuberculosis. Whilst a number of potent inhibitors of the Mycobacterium tuberculosis enzyme based on a 3-dehydroquinate core have been identified, they generally show little or no in vivo activity, and were synthetically complex to prepare. This report describes studies to develop tractable and drug-like aromatic analogues of the most potent inhibitors. A range of carbon-carbon linked biaryl analogues were prepared to investigate the effect of hydrogen bond acceptor and donor patterns on inhibition. These exhibited inhibitory activity in the high-micromolar range. The addition of flexible linkers in the compounds led to the identification of more potent 3-nitrobenzylgallate- and 5-aminoisophthalate-based analogues.

PubMed: 25234229
DOI: 10.1002/cmdc.201402298

実験手法

X-RAY DIFFRACTION (2.8 Å)