4JNK

Lactate Dehydrogenase A in complex with inhibitor compound 22

Summary for 4JNK

• Entry DOI: 10.2210/pdb4jnk/pdb
• Descriptor: L-lactate dehydrogenase A chain, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (7 entities in total)
• Functional Keywords: alpha-beta, pyruvate reductase and lactate dehydrogenase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00338
• Total number of polymer chains: 4
• Total formula weight: 151742.04

Authors

Eigenbrot, C.,Ultsch, M. (deposition date: 2013-03-15, release date: 2013-05-22, Last modification date: 2023-11-15)

Primary citation

Dragovich, P.S.,Fauber, B.P.,Corson, L.B.,Ding, C.Z.,Eigenbrot, C.,Ge, H.,Giannetti, A.M.,Hunsaker, T.,Labadie, S.,Liu, Y.,Malek, S.,Pan, B.,Peterson, D.,Pitts, K.,Purkey, H.E.,Sideris, S.,Ultsch, M.,Vanderporten, E.,Wei, B.,Xu, Q.,Yen, I.,Yue, Q.,Zhang, H.,Zhang, X.
Identification of substituted 2-thio-6-oxo-1,6-dihydropyrimidines as inhibitors of human lactate dehydrogenase.
Bioorg.Med.Chem.Lett., 23:3186-3194, 2013

PubMed Abstract: A novel 2-thio-6-oxo-1,6-dihydropyrimidine-containing inhibitor of human lactate dehydrogenase (LDH) was identified by high-throughput screening (IC50=8.1 μM). Biochemical, surface plasmon resonance, and saturation transfer difference NMR experiments indicated that the compound specifically associated with human LDHA in a manner that required simultaneous binding of the NADH co-factor. Structural variation of the screening hit resulted in significant improvements in LDHA biochemical inhibition activity (best IC50=0.48 μM). A crystal structure of an optimized compound bound to human LDHA was obtained and explained many of the observed structure-activity relationships.

PubMed: 23628333
DOI: 10.1016/j.bmcl.2013.04.001

Experimental method

X-RAY DIFFRACTION (1.896 Å)