4nog

Crystal structure of a putative ornithine aminotransferase from Toxoplasma gondii ME49 in complex with pyrodoxal-5'-phosphate

spinqualitylabelsall models 4nog, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4nog is a 2 chain structure with sequence from Toxoplasma gondii ME49. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.2Å Ligands: ACT, BME, BTB, PEG, PLP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function S8EY38_TOXGM Publication Abstract from PubMed Toxoplasma gondii, an Apicomplexan parasite, causes significant morbidity and mortality, including severe disease in immunocompromised hosts and devastating congenital disease, with no effective treatment for the bradyzoite stage. To address this, we used the Tropical Disease Research database, crystallography, molecular modeling, and antisense to identify and characterize a range of potential therapeutic targets for toxoplasmosis. Phosphoglycerate mutase II (PGMII), nucleoside diphosphate kinase (NDK), ribulose phosphate 3-epimerase (RPE), ribose-5-phosphate isomerase (RPI), and ornithine aminotransferase (OAT) were structurally characterized. Crystallography revealed insights into the overall structure, protein oligomeric states and molecular details of active sites important for ligand recognition. Literature and molecular modeling suggested potential inhibitors and druggability. The targets were further studied with vivoPMO to interrupt enzyme synthesis, identifying the targets as potentially important to parasitic replication and, therefore, of therapeutic interest. Targeted vivoPMO resulted in statistically significant perturbation of parasite replication without concomitant host cell toxicity, consistent with a previous CRISPR/Cas9 screen showing PGM, RPE, and RPI contribute to parasite fitness. PGM, RPE, and RPI have the greatest promise for affecting replication in tachyzoites. These targets are shared between other medically important parasites and may have wider therapeutic potential. CSGID Solves Structures and Identifies Phenotypes for Five Enzymes in Toxoplasma gondii.,Lykins JD, Filippova EV, Halavaty AS, Minasov G, Zhou Y, Dubrovska I, Flores KJ, Shuvalova LA, Ruan J, El Bissati K, Dovgin S, Roberts CW, Woods S, Moulton JD, Moulton H, McPhillie MJ, Muench SP, Fishwick CWG, Sabini E, Shanmugam D, Roos DS, McLeod R, Anderson WF, Ngo HM Front Cell Infect Microbiol. 2018 Oct 5;8:352. doi: 10.3389/fcimb.2018.00352. , eCollection 2018. PMID:30345257 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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