4M49

Lactate Dehydrogenase A in complex with a substituted pyrazine inhibitor compound 18

4M49 の概要

• エントリーDOI: 10.2210/pdb4m49/pdb
• 関連するPDBエントリー: 4JNK
• 分子名称: L-lactate dehydrogenase A chain, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (7 entities in total)
• 機能のキーワード: dehydrogenase/reductase, nicotinamide adenine dinucleotide nadh, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 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: 151275.29

構造登録者

Eigenbrot, C.,Ultsch, M. (登録日: 2013-08-06, 公開日: 2013-09-04, 最終更新日: 2023-11-15)

主引用文献

Fauber, B.P.,Dragovich, P.S.,Chen, J.,Corson, L.B.,Ding, C.Z.,Eigenbrot, C.,Giannetti, A.M.,Hunsaker, T.,Labadie, S.,Liu, Y.,Liu, Y.,Malek, S.,Peterson, D.,Pitts, K.,Sideris, S.,Ultsch, M.,Vanderporten, E.,Wang, J.,Wei, B.,Yen, I.,Yue, Q.
Identification of 2-amino-5-aryl-pyrazines as inhibitors of human lactate dehydrogenase.
Bioorg.Med.Chem.Lett., 23:5533-5539, 2013

PubMed Abstract: A 2-amino-5-aryl-pyrazine was identified as an inhibitor of human lactate dehydrogenase A (LDHA) via a biochemical screening campaign. Biochemical and biophysical experiments demonstrated that the compound specifically interacted with human LDHA. Structural variation of the screening hit resulted in improvements in LDHA biochemical inhibition and pharmacokinetic properties. A crystal structure of an improved compound bound to human LDHA was also obtained and it explained many of the observed structure-activity relationships.

PubMed: 24012183
DOI: 10.1016/j.bmcl.2013.08.060

実験手法

X-RAY DIFFRACTION (2.052 Å)