5esd

Crystal Structure of M. tuberculosis MenD bound to ThDP and Mn2+

spinqualitylabelsall models 5esd, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5esd 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: MN, TPP Related: 5erx, 5ery, 5esu, 5eso, 5ess Gene: menD, Rv0555 (MYCTU) Activity: 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase, with EC number 2.2.1.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MEND_MYCTU] Catalyzes the thiamine diphosphate-dependent decarboxylation of 2-oxoglutarate and the subsequent addition of the resulting succinic semialdehyde-thiamine pyrophosphate anion to isochorismate to yield 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC). Publication Abstract from PubMed Menaquinone (MQ) is an essential component of the respiratory chains of many pathogenic organisms, including Mycobacterium tuberculosis (Mtb). The first committed step in MQ biosynthesis is catalyzed by 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate synthase (MenD), a thiamin diphosphate (ThDP)-dependent enzyme. Catalysis proceeds through two covalent intermediates as the substrates 2-oxoglutarate and isochorismate are successively added to the cofactor before final cleavage of the product. We have determined a series of crystal structures of Mtb-MenD that map the binding of both substrates, visualizing each step in the MenD catalytic cycle, including both intermediates. ThDP binding induces a marked asymmetry between the coupled active sites of each dimer, and possible mechanisms of communication can be identified. The crystal structures also reveal conformational features of the two intermediates that facilitate reaction but prevent premature product release. These data fully map chemical space to inform early-stage drug discovery targeting MenD. Structural Views along the Mycobacterium tuberculosis MenD Reaction Pathway Illuminate Key Aspects of Thiamin Diphosphate-Dependent Enzyme Mechanisms.,Jirgis EN, Bashiri G, Bulloch EM, Johnston JM, Baker EN Structure. 2016 Jul 6;24(7):1167-77. doi: 10.1016/j.str.2016.04.018. Epub 2016, Jun 9. PMID:27291649 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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