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]

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.
PDB ID: 4KIUDownload
MMDB ID: 119360
PDB Deposition Date: 2013/5/2
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 4KIU: dodecameric; determined by author
Molecular Components in 4KIU
Label Count Molecule
Proteins (12 molecules)
3-dehydroquinate Dehydratase
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB