2ixc

RmlC M. tuberculosis with dTDP-rhamnose

spinqualitylabelsall models 2ixc, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ixc is a 4 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. Ligands: TRH Related: 1pm7, 1upi, 2ixh, 2ixi, 2ixj, 2ixk, 2ixl Activity: dTDP-4-dehydrorhamnose 3,5-epimerase, with EC number 5.1.3.13 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [RMLC_MYCTU] Catalyzes the epimerization of the C3' and C5'positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose. Involved in the biosynthesis of the dTDP-L-rhamnose which is a component of the critical linker, D-N-acetylglucosamine-L-rhamnose disaccharide, which connects the galactan region of arabinogalactan to peptidoglycan via a phosphodiester linkage. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The striking feature of carbohydrates is their constitutional, conformational and configurational diversity. Biology has harnessed this diversity and manipulates carbohydrate residues in a variety of ways, one of which is epimerization. RmlC catalyzes the epimerization of the C3' and C5' positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose. RmlC is the third enzyme of the rhamnose pathway, and represents a validated anti-bacterial drug target. Although several structures of the enzyme have been reported, the mechanism and the nature of the intermediates have remained obscure. Despite its relatively small size (22 kDa), RmlC catalyzes four stereospecific proton transfers and the substrate undergoes a major conformational change during the course of the transformation. Here we report the structure of RmlC from several organisms in complex with product and product mimics. We have probed site-directed mutants by assay and by deuterium exchange. The combination of structural and biochemical data has allowed us to assign key residues and identify the conformation of the carbohydrate during turnover. Clear knowledge of the chemical structure of RmlC reaction intermediates may offer new opportunities for rational drug design. RmlC, a C3' and C5' carbohydrate epimerase, appears to operate via an intermediate with an unusual twist boat conformation.,Dong C, Major LL, Srikannathasan V, Errey JC, Giraud MF, Lam JS, Graninger M, Messner P, McNeil MR, Field RA, Whitfield C, Naismith JH J Mol Biol. 2007 Jan 5;365(1):146-59. Epub 2006 Sep 29. PMID:17046787 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RmlC

Proteopedia Page Contributors and Editors (what is this?)

OCA