4KI7
Design and structural analysis of aromatic inhibitors of type II dehydroquinase from Mycobacterium tuberculosis - compound 41c [3-hydroxy-5-(3-nitrophenoxy)benzoic acid]
Summary for 4KI7
| Entry DOI | 10.2210/pdb4ki7/pdb |
| Descriptor | 3-dehydroquinate dehydratase, 3-hydroxy-5-(3-nitrophenoxy)benzoic acid (3 entities in total) |
| Functional Keywords | dhqase, dehydratase, lyase-lyase inhibitor complex, lyase/lyase inhibitor |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 24 |
| Total formula weight | 404089.64 |
| Authors | Dias, M.V.B.,Howard, N.G.,Blundell, T.L.,Abell, C. (deposition date: 2013-05-01, 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 Cited by 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: 25234229DOI: 10.1002/cmdc.201402298 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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