7dbk | pdb_00007dbk

Crystal structure of human LDHB in complex with NADH

spinqualitylabelsall models 7dbk, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7dbk is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, NAI Activity: L-lactate dehydrogenase, with EC number 1.1.1.27 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Lactate dehydrogenase (LDH) catalyses the conversion of pyruvate to lactate and NADH to NAD(+); it has two isoforms, LDHA and LDHB. LDHA is a promising target for cancer therapy, whereas LDHB is necessary for basal autophagy and cancer cell proliferation in oxidative and glycolytic cancer cells. To the best of our knowledge, selective inhibitors for LDHB have not yet been reported. Here, we developed a high-throughput mass spectrometry screening system using an LDHB enzyme assay by detecting NADH and NAD(+). As a result, we identified a small-molecule LDHB selective inhibitor AXKO-0046, an indole derivative. This compound exhibited uncompetitive LDHB inhibition (EC50 = 42 nM). X-ray crystallography revealed that AXKO-0046 bound to the potential allosteric site away from the LDHB catalytic active site, suggesting that targeting the tetramerisation interface of the two dimers is critical for the enzymatic activity. AXKO-0046 and its derivatives can be used to validate LDHB-associated pathways in cancer metabolism. Identification of the first highly selective inhibitor of human lactate dehydrogenase B.,Shibata S, Sogabe S, Miwa M, Fujimoto T, Takakura N, Naotsuka A, Kitamura S, Kawamoto T, Soga T Sci Rep. 2021 Nov 1;11(1):21353. doi: 10.1038/s41598-021-00820-7. PMID:34725423 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA