3rim

Crystal structure of mycobacterium tuberculosis Transketolase (Rv1449c)

spinqualitylabelsall models 3rim, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3rim is a 4 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, MG, TPP Gene: tkt, Rv1449c, MT1496, MTCY493.05 (MYCTU) Activity: Transketolase, with EC number 2.2.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TKT_MYCTU] Catalyzes the reversible transfer of a two-carbon ketol group from sedoheptulose-7-phosphate to glyceraldehyde-3-phosphate, producing xylulose-5-phosphate and ribose-5-phosphate. Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.[REFERENCE:3] Publication Abstract from PubMed The transketolase (TKT) enzyme in Mycobacterium tuberculosis represents a novel drug target for tuberculosis treatment and has low homology with the orthologous human enzyme. Here, we report on the structural and kinetic characterization of the transketolase from M. tuberculosis (TBTKT), a homodimer whose monomers each comprise 700 amino acids. We show that TBTKT catalyses the oxidation of donor sugars xylulose-5-phosphate and fructose-6-phosphate as well as the reduction of the acceptor sugar ribose-5-phosphate. An invariant residue of the TKT consensus sequence required for thiamine cofactor binding is mutated in TBTKT; yet its catalytic activities are unaffected, and the 2.5 A resolution structure of full-length TBTKT provides an explanation for this. Key structural differences between the human and mycobacterial TKT enzymes that impact both substrate and cofactor recognition and binding were uncovered. These changes explain the kinetic differences between TBTKT and its human counterpart, and their differential inhibition by small molecules. The availability of a detailed structural model of TBTKT will enable differences between human and M. tuberculosis TKT structures to be exploited to design selective inhibitors with potential antitubercular activity. Structure and function of the transketolase from Mycobacterium tuberculosis and comparison with the human enzyme.,Fullam E, Pojer F, Bergfors T, Jones TA, Cole ST Open Biol. 2012 Jan;2(1):110026. doi: 10.1098/rsob.110026. PMID:22645655 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transketolase 3D structures

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