3vw9

Human Glyoxalase I with an N-hydroxypyridone inhibitor

spinqualitylabelsall models 3vw9, resolution 1.47Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3vw9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.47Å Ligands: EPE, HPJ, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LGUL_HUMAN Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione. Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B. Publication Abstract from PubMed We conducted a high throughput screening for glyoxalase I (GLO1) inhibitors and identified 4,6-diphenyl-N-hydroxypyridone as a lead compound. Using a binding model of the lead and public X-ray coordinates of GLO1 enzymes complexed with glutathione analogues, we designed 4-(7-azaindole)-substituted 6-phenyl-N-hydroxypyridones. 7-Azaindole's 7-nitrogen was expected to interact with a water network, resulting in an interaction with the protein. We validated this inhibitor design by comparing its structure-activity relationship (SAR) with that of corresponding indole derivatives, by analyzing the binding mode with X-ray crystallography and by evaluating its thermodynamic binding parameters. Design and evaluation of azaindole-substituted N-hydroxypyridones as glyoxalase I inhibitors.,Chiba T, Ohwada J, Sakamoto H, Kobayashi T, Fukami TA, Irie M, Miura T, Ohara K, Koyano H Bioorg Med Chem Lett. 2012 Dec 15;22(24):7486-9. doi: 10.1016/j.bmcl.2012.10.045., Epub 2012 Oct 17. PMID:23122816 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glyoxalase 3D structures

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