4R68

Lactate Dehydrogenase in complex with inhibitor compound 31

Summary for 4R68

• Entry DOI: 10.2210/pdb4r68/pdb
• Related: 4R69
• Descriptor: L-lactate dehydrogenase A chain, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (6 entities in total)
• Functional Keywords: oxidoreductase, nicotinamide adenine dinucleaotide
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00338
• Total number of polymer chains: 4
• Total formula weight: 152372.55

Authors

Eigenbrot, C.,Ultsch, M. (deposition date: 2014-08-22, release date: 2014-12-24, Last modification date: 2023-09-20)

Primary citation

Labadie, S.,Dragovich, P.S.,Chen, J.,Fauber, B.P.,Boggs, J.,Corson, L.B.,Ding, C.Z.,Eigenbrot, C.,Ge, H.,Ho, Q.,Lai, K.W.,Ma, S.,Malek, S.,Peterson, D.,Purkey, H.E.,Robarge, K.,Salphati, L.,Sideris, S.,Ultsch, M.,VanderPorten, E.,Wei, B.,Xu, Q.,Yen, I.,Yue, Q.,Zhang, H.,Zhang, X.,Zhou, A.
Optimization of 5-(2,6-dichlorophenyl)-3-hydroxy-2-mercaptocyclohex-2-enones as potent inhibitors of human lactate dehydrogenase.
Bioorg.Med.Chem.Lett., 25:75-82, 2014

PubMed Abstract: Optimization of 5-(2,6-dichlorophenyl)-3-hydroxy-2-mercaptocyclohex-2-enone using structure-based design strategies resulted in inhibitors with considerable improvement in biochemical potency against human lactate dehydrogenase A (LDHA). These potent inhibitors were typically selective for LDHA over LDHB isoform (4–10 fold) and other structurally related malate dehydrogenases, MDH1 and MDH2 (>500 fold). An X-ray crystal structure of enzymatically most potent molecule bound to LDHA revealed two additional interactions associated with enhanced biochemical potency.

PubMed: 25466195
DOI: 10.1016/j.bmcl.2014.11.008

Experimental method

X-RAY DIFFRACTION (2.112 Å)