2af6

Crystal structure of Mycobacterium tuberculosis Flavin dependent thymidylate synthase (Mtb ThyX) in the presence of co-factor FAD and substrate analog 5-Bromo-2'-Deoxyuridine-5'-Monophosphate (BrdUMP)Crystal structure of Mycobacterium tuberculosis Flavin dependent thymidylate synthase (Mtb ThyX) in the presence of co-factor FAD and substrate analog 5-Bromo-2'-Deoxyuridine-5'-Monophosphate (BrdUMP)

Structural highlights 2af6 is a 8 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.01Å Ligands: , , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function THYX_MYCTU Catalyzes the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate (By similarity). 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 A novel flavin-dependent thymidylate synthase was identified recently as an essential gene in many archaebacteria and some pathogenic eubacteria. This enzyme, ThyX, is a potential antibacterial drug target, since humans and most eukaryotes lack the thyX gene and depend upon the conventional thymidylate synthase (TS) for their dTMP requirements. We have cloned and overexpressed the thyX gene (Rv2754c) from Mycobacterium tuberculosis in Escherichia coli. The M.tuberculosis ThyX (MtbThyX) enzyme complements the E.coli chi2913 strain that lacks its conventional TS activity. The crystal structure of the homotetrameric MtbThyX was determined in the presence of the cofactor FAD and the substrate analog, 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdUMP). In the active site, which is formed by three monomers, FAD is bound in an extended conformation with the adenosine ring in a deep pocket and BrdUMP in a closed conformation near the isoalloxazine ring. Structure-based mutational studies have revealed a critical role played by residues Lys165 and Arg168 in ThyX activity, possibly by governing access to the carbon atom to be methylated of a totally buried substrate dUMP. Structure of the Mycobacterium tuberculosis flavin dependent thymidylate synthase (MtbThyX) at 2.0A resolution.,Sampathkumar P, Turley S, Ulmer JE, Rhie HG, Sibley CH, Hol WG J Mol Biol. 2005 Oct 7;352(5):1091-104. PMID:16139296 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Protein structures Thymidylate synthase 3D structures

spinqualitylabelsall models 2af6, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image