4R68

Lactate Dehydrogenase in complex with inhibitor compound 31

4R68 の概要

• エントリーDOI: 10.2210/pdb4r68/pdb
• 関連するPDBエントリー: 4R69
• 分子名称: L-lactate dehydrogenase A chain, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (6 entities in total)
• 機能のキーワード: oxidoreductase, nicotinamide adenine dinucleaotide
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00338
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 152372.55

構造登録者

Eigenbrot, C.,Ultsch, M. (登録日: 2014-08-22, 公開日: 2014-12-24, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.112 Å)