5ESU
Crystal Structure of M. tuberculosis MenD bound to Mg2+ and Covalent Intermediate II (a ThDP + de-carboxylated 2-oxoglutarate + Isochorismate adduct)
Summary for 5ESU
| Entry DOI | 10.2210/pdb5esu/pdb |
| Related | 5ERX 5ERY 5ESD 5ESO 5ESS |
| Descriptor | 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase, MAGNESIUM ION, FORMIC ACID, ... (6 entities in total) |
| Functional Keywords | menaquinone biosynthesis, mend, 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate synthase, thiamin-diphosphate dependent enzyme, pyruvate oxidase family, transferase |
| Biological source | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Total number of polymer chains | 4 |
| Total formula weight | 242104.18 |
| Authors | Johnston, J.M.,Jirgis, E.N.M.,Bashiri, G.,Bulloch, E.M.M.,Baker, E.N. (deposition date: 2015-11-17, release date: 2016-06-22, Last modification date: 2024-05-01) |
| Primary citation | Jirgis, E.N.,Bashiri, G.,Bulloch, E.M.,Johnston, J.M.,Baker, E.N. Structural Views along the Mycobacterium tuberculosis MenD Reaction Pathway Illuminate Key Aspects of Thiamin Diphosphate-Dependent Enzyme Mechanisms. Structure, 24:1167-1177, 2016 Cited by PubMed Abstract: 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. PubMed: 27291649DOI: 10.1016/j.str.2016.04.018 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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