Mycobacterium tuberculosis RmlC epimerase (Rv3465): a promising drug-target structure in the rhamnose pathway

• Published in: Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2004-05, Vol.60 (5), p.895-902
• Main Authors: Kantardjieff, Katherine A., Kim, Chang-Yub, Naranjo, Cleo, Waldo, Geoffry S., Lekin, Timothy, Segelke, Brent W., Zemla, Adam, Park, Min S., Terwilliger, Thomas C., Rupp, Bernhard
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites; Carbohydrate Epimerases - chemistry; Carbohydrate Epimerases - metabolism; Crystallography, X-Ray; Dimerization; Drug Design; drug-target structure; dTDP-4-keto-6-deoxyglucose epimerase; Genomics; International Cooperation; Models, Molecular; Molecular Sequence Data; Mycobacterium tuberculosis; Mycobacterium tuberculosis - enzymology; Mycobacterium tuberculosis - metabolism; Pilot Projects; Protein Conformation; Rhamnose - metabolism; rhamnose pathway; RmlC; Rv3456; Sequence Homology, Amino Acid; Structural Homology, Protein
• ISSN: 1399-0047; 0907-4449; 1399-0047
• DOI: 10.1107/S0907444904005323

The Mycobacterium tuberculosis rmlC gene encodes dTDP‐4‐­keto‐6‐deoxyglucose epimerase, the third enzyme in the M. tuberculosis dTDP‐l‐rhamnose pathway which is essential for mycobacterial cell‐wall synthesis. Because it is structurally unique, highly substrate‐specific and does not require a cofactor, RmlC is considered to be the most promising drug target in the pathway, and the M. tuberculosisrmlC gene was selected in the initial round of TB Structural Genomics Consortium targets for structure determination. The 1.7 Å native structure determined by the consortium facilities is reported and implications for in silico screening of ligands for structure‐guided drug design are discussed.