4KIU

Design and structural analysis of aromatic inhibitors of type II dehydroquinate dehydratase from Mycobacterium tuberculosis - compound 49d [5-[(3-nitrobenzyl)oxy]benzene-1,3-dicarboxylic acid]

Summary for 4KIU

• Entry DOI: 10.2210/pdb4kiu/pdb
• Related: 4KI7 4KIJ 4KIM 4KIW 4KL9 4KLX 4KM0 4KM2
• Descriptor: 3-dehydroquinate dehydratase, 5-[(3-nitrobenzyl)oxy]benzene-1,3-dicarboxylic acid (3 entities in total)
• Functional Keywords: dehydratase, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 24
• Total formula weight: 405014.44

Authors

Dias, M.V.B.,Howard, N.G.,Blundell, T.L.,Abell, C. (deposition date: 2013-05-02, release date: 2014-05-14, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)