2y85 | pdb_00002y85

CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS PHOSPHORIBOSYL ISOMERASE WITH BOUND RCDRP

spinqualitylabelsall models 2y85, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2y85 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: 137, CL, NA Related: 2y89, 2y88 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HIS4_MYCTU] Involved in both the histidine and tryptophan biosynthetic pathways. Publication Abstract from PubMed In histidine and tryptophan biosynthesis, two related isomerization reactions are generally catalyzed by two specific single-substrate enzymes (HisA and TrpF), sharing a similar (beta/alpha)(8)-barrel scaffold. However, in some actinobacteria, one of the two encoding genes (trpF) is missing and the two reactions are instead catalyzed by one bisubstrate enzyme (PriA). To unravel the unknown mechanism of bisubstrate specificity, we used the Mycobacterium tuberculosis PriA enzyme as a model. Comparative structural analysis of the active site of the enzyme showed that PriA undergoes a reaction-specific and substrate-induced metamorphosis of the active site architecture, demonstrating its unique ability to essentially form two different substrate-specific actives sites. Furthermore, we found that one of the two catalytic residues in PriA, which are identical in both isomerization reactions, is recruited by a substrate-dependent mechanism into the active site to allow its involvement in catalysis. Comparison of the structural data from PriA with one of the two single-substrate enzymes (TrpF) revealed substantial differences in the active site architecture, suggesting independent evolution. To support these observations, we identified six small molecule compounds that inhibited both PriA-catalyzed isomerization reactions but had no effect on TrpF activity. Our data demonstrate an opportunity for organism-specific inhibition of enzymatic catalysis by taking advantage of the distinct ability for bisubstrate catalysis in the M. tuberculosis enzyme. Bisubstrate specificity in histidine/tryptophan biosynthesis isomerase from Mycobacterium tuberculosis by active site metamorphosis.,Due AV, Kuper J, Geerlof A, Kries JP, Wilmanns M Proc Natl Acad Sci U S A. 2011 Feb 14. PMID:21321225 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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