4qo8

Lactate Dehydrogenase A in complex with substituted 3-Hydroxy-2-mercaptocyclohex-2-enone compound 104

spinqualitylabelsall models 4qo8, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qo8 is a 4 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 2.001Å Ligands: 36U, EPE, LAC, NAI, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease LDHA_HUMAN Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:612933. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue. Function LDHA_HUMAN Publication Abstract from PubMed A novel class of 3-hydroxy-2-mercaptocyclohex-2-enone-containing inhibitors of human lactate dehydrogenase (LDH) was identified through a high-throughput screening approach. Biochemical and surface plasmon resonance experiments performed with a screening hit (LDHA IC50=1.7muM) indicated that the compound specifically associated with human LDHA in a manner that required simultaneous binding of the NADH co-factor. Structural variation of this screening hit resulted in significant improvements in LDHA biochemical inhibition activity (best IC50=0.18muM). Two crystal structures of optimized compounds bound to human LDHA were obtained and explained many of the observed structure-activity relationships. In addition, an optimized inhibitor exhibited good pharmacokinetic properties after oral administration to rats (F=45%). Identification of substituted 3-hydroxy-2-mercaptocyclohex-2-enones as potent inhibitors of human lactate dehydrogenase.,Dragovich PS, Fauber BP, Boggs J, Chen J, Corson LB, Ding CZ, Eigenbrot C, Ge H, Giannetti AM, Hunsaker T, Labadie S, Li C, Liu Y, Liu Y, Ma S, Malek S, Peterson D, Pitts KE, Purkey HE, Robarge K, Salphati L, Sideris S, Ultsch M, VanderPorten E, Wang J, Wei B, Xu Q, Yen I, Yue Q, Zhang H, Zhang X, Zhou A Bioorg Med Chem Lett. 2014 Aug 15;24(16):3764-71. doi:, 10.1016/j.bmcl.2014.06.076. Epub 2014 Jul 1. PMID:25037916 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lactate dehydrogenase 3D structures

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