8ofw

Crystal structure of the full-length dihydroorotate dehydrogenase from Mycobacterium tuberculosis

spinqualitylabelsall models 8ofw, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ofw is a 2 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 3.8Å Ligands: FMN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PYRD_MYCTU Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. Publication Abstract from PubMed Mycobacterium tuberculosis (MTB) is the etiologic agent of tuberculosis (TB), an ancient disease which causes 1.5 million deaths worldwide. Dihydroorotate dehydrogenase (DHODH) is a key enzyme of the MTB de novo pyrimidine biosynthesis pathway, and it is essential for MTB growth in vitro, hence representing a promising drug target. We present: (i) the biochemical characterization of the full-length MTB DHODH, including the analysis of the kinetic parameters, and (ii) the previously unreleased crystal structure of the protein that allowed us to rationally screen our in-house chemical library and identify the first selective inhibitor of mycobacterial DHODH. The inhibitor has fluorescence properties, potentially instrumental to in cellulo imaging studies, and exhibits an IC(50) value of 43 mum, paving the way to hit-to-lead process. Biochemical characterization of Mycobacterium tuberculosis dihydroorotate dehydrogenase and identification of a selective inhibitor.,Alberti M, Sainas S, Ronchi E, Lolli ML, Boschi D, Rizzi M, Ferraris DM, Miggiano R FEBS Lett. 2023 Aug;597(16):2119-2132. doi: 10.1002/1873-3468.14680. Epub 2023 , Jun 15. PMID:37278160 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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