4M49

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

Summary for 4M49

• Entry DOI: 10.2210/pdb4m49/pdb
• Related: 4JNK
• Descriptor: L-lactate dehydrogenase A chain, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (7 entities in total)
• Functional Keywords: dehydrogenase/reductase, nicotinamide adenine dinucleotide nadh, 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: 151275.29

Authors

Eigenbrot, C.,Ultsch, M. (deposition date: 2013-08-06, release date: 2013-09-04, Last modification date: 2023-11-15)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.052 Å)