Structural highlights
4kiu is a 24 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Related: | 4ki7, 4kij, 4kim, 4kiw, 4kl9, 4klx, 4km0, 4km2 |
| Gene: | aroD, aroQ, MT2612, MTCY159.19, Rv2537c ("Bacillus tuberculosis" (Zopf 1883) Klein 1884) |
| Activity: | 3-dehydroquinate dehydratase, with EC number 4.2.1.10 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[AROQ_MYCTU] Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169]
Publication Abstract from PubMed
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.
Design and Structural Analysis of Aromatic Inhibitors of Type II Dehydroquinase from Mycobacterium tuberculosis.,Howard NI, Dias MV, Peyrot F, Chen L, Schmidt MF, Blundell TL, Abell C ChemMedChem. 2015 Jan;10(1):116-33. doi: 10.1002/cmdc.201402298. Epub 2014 Sep, 18. PMID:25234229[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Howard NI, Dias MV, Peyrot F, Chen L, Schmidt MF, Blundell TL, Abell C. Design and Structural Analysis of Aromatic Inhibitors of Type II Dehydroquinase from Mycobacterium tuberculosis. ChemMedChem. 2015 Jan;10(1):116-33. doi: 10.1002/cmdc.201402298. Epub 2014 Sep, 18. PMID:25234229 doi:http://dx.doi.org/10.1002/cmdc.201402298
