6T8P

HKATII IN COMPLEX WITH LIGAND (2R)-N-benzyl-1-[6-methyl-5-(oxan-4-yl)-7-oxo-6H,7H-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]pyrrolidine-2-carboxamide

Summary for 6T8P

• Entry DOI: 10.2210/pdb6t8p/pdb
• Descriptor: Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial, 3,5-bis(fluoranyl)-~{N}-[5-[(2~{R})-2-(3-fluorophenyl)-3-methyl-butyl]-1,3,4-thiadiazol-2-yl]benzenesulfonamide, IODIDE ION, ... (5 entities in total)
• Functional Keywords: alpha & beta protein, plp-dependent transferase, kat ii, kynurenine am, proteros biostructures gmbh, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 104822.79

Authors

Blaesse, M.,Venalainen, J. (deposition date: 2019-10-24, release date: 2020-03-04, Last modification date: 2024-01-24)

Primary citation

Kalliokoski, T.,Rummakko, P.,Rantanen, M.,Blaesse, M.,Augustin, M.,Ummenthala, G.R.,Choudhary, S.,Venalainen, J.
Discovery of sulfonamides and 9-oxo-2,8-diazaspiro[5,5]undecane-2-carboxamides as human kynurenine aminotransferase 2 (KAT2) inhibitors.
Bioorg.Med.Chem.Lett., 30:127060-127060, 2020

PubMed Abstract: Human kynurenine aminotransferase 2 (KAT2) inhibitors could be potentially used to treat the cognitive deficits associated with bipolar disease and schizophrenia. Although, there has been active drug research activity by several industrial and academic groups in developing KAT2 inhibitors over the years, no such compound has proceeded to the clinics. Here, we report two different chemical series of reversible KAT2 inhibitors with sub-micromolar activities. The first series was identified by a high-throughput screening of a diverse random library and the second one by structure-based virtual screening. Two novel crystal structures of KAT2 complexed with different reversible inhibitors were also deposited to the Protein databank which could be useful for future drug discovery efforts.

PubMed: 32113843
DOI: 10.1016/j.bmcl.2020.127060

Experimental method

X-RAY DIFFRACTION (2.02 Å)