title: Mycobacterium tuberculosis RmlC epimerase (Rv3465): a promising drug-target structure in the rhamnose pathway.
abstract: 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. tuberculosis rmlC gene was selected in the initial round of TB Structural Genomics Consortium targets for structure determination. The 1.7 A native structure determined by the consortium facilities is reported and implications for in silico screening of ligands for structure-guided drug design are discussed.
authors.affiliation: Department of Chemistry and Biochemistry and W M Keck Foundation Center for Molecular Structure, California State University Fullerton, Fullerton, CA 92834, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Kantardjieff
authors.forename: Chang Yub
authors.initials: CY
authors.lastname: Kim
authors.forename: Cleo
authors.initials: C
authors.lastname: Naranjo
authors.forename: Geoffry S
authors.initials: GS
authors.lastname: Waldo
authors.forename: Timothy
authors.initials: T
authors.lastname: Lekin
authors.forename: Brent W
authors.initials: BW
authors.lastname: Segelke
authors.forename: Adam
authors.initials: A
authors.lastname: Zemla
authors.forename: Min S
authors.initials: MS
authors.lastname: Park
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Terwilliger
authors.forename: Bernhard
authors.initials: B
authors.lastname: Rupp
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002238:Carbohydrate Epimerases / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D015195:Drug Design; D023281:Genomics; D007391:International Cooperation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000378:metabolism; D010865:Pilot Projects; D011487:Protein Conformation; D012210:Rhamnose / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D001426:Bacterial Proteins; D002237:Carbohydrate Dehydrogenases
chemical_list: D002238:Carbohydrate Epimerases; D012210:Rhamnose; C020092:dTDP-4-ketorhamnose 3,5-epimerase; D001426:Bacterial Proteins; D002237:Carbohydrate Dehydrogenases