6sbv
From Proteopedia
X-ray Structure of Human LDH-A with an Allosteric Inhibitor (Compound 7)
Structural highlights
DiseaseLDHA_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.[1] FunctionPublication Abstract from PubMedLactate dehydrogenase A (LDHA) is frequently overexpressed in tumors, thereby sustaining high glycolysis rates, tumor growth, and chemoresistance. High-throughput screening resulted in the identification of phthalimide and dibenzofuran derivatives as novel lactate dehydrogenase inhibitors, selectively inhibiting the activity of the LDHA isoenzyme. Cocrystallization experiments confirmed target engagement in addition to demonstrating binding to a novel allosteric binding site present in all four LDHA subunits of the LDH5 homotetramer. Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A.,Friberg A, Rehwinkel H, Nguyen D, Putter V, Quanz M, Weiske J, Eberspacher U, Heisler I, Langer G ACS Omega. 2020 May 27;5(22):13034-13041. doi: 10.1021/acsomega.0c00715., eCollection 2020 Jun 9. PMID:32548488[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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