2ABJ

Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.

2ABJ の概要

• エントリーDOI: 10.2210/pdb2abj/pdb
• 分子名称: Branched-chain-amino-acid aminotransferase, cytosolic, N'-(5-CHLOROBENZOFURAN-2-CARBONYL)-2-(TRIFLUOROMETHYL)BENZENESULFONOHYDRAZIDE, PYRIDOXAL-5'-PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: branched-chain-amino-acid aminotransferase, cytosolic, pyridoxal-phosphate-dependent aminotransferase, plp-lys220 schiff base, inhibitor-bound, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P54687
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 167079.43

構造登録者

Ohren, J.F.,Moreland, D.W.,Rubin, J.R.,Hu, H.L.,McConnell, P.C.,Mistry, A.,Mueller, W.T.,Scholten, J.D.,Hasemann, C.H. (登録日: 2005-07-15, 公開日: 2006-06-27, 最終更新日: 2025-03-26)

主引用文献

Hu, L.Y.,Boxer, P.A.,Kesten, S.R.,Lei, H.J.,Wustrow, D.J.,Moreland, D.W.,Zhang, L.,Ahn, K.,Ryder, T.R.,Liu, X.,Rubin, J.R.,Fahnoe, K.,Carroll, R.T.,Dutta, S.,Fahnoe, D.C.,Probert, A.W.,Roof, R.L.,Rafferty, M.F.,Kostlan, C.R.,Scholten, J.D.,Hood, M.,Ren, X.D.,Schielke, G.P.,Su, T.Z.,Taylor, C.P.,Mistry, A.,McConnell, P.,Hasemann, C.,Ohren, J.
The design and synthesis of human branched-chain amino acid aminotransferase inhibitors for treatment of neurodegenerative diseases.
Bioorg.Med.Chem.Lett., 16:2337-2340, 2006

PubMed Abstract: The inhibition of the cytosolic isoenzyme BCAT that is expressed specifically in neuronal tissue is likely to be useful for the treatment of neurodegenerative and other neurological disorders where glutamatergic mechanisms are implicated. Compound 2 exhibited an IC50 of 0.8 microM in the hBCATc assays; it is an active and selective inhibitor. Inhibitor 2 also blocked calcium influx into neuronal cells following inhibition of glutamate uptake, and demonstrated neuroprotective efficacy in vivo. SAR, pharmacology, and the crystal structure of hBCATc with inhibitor 2 are described.

PubMed: 16143519
DOI: 10.1016/j.bmcl.2005.07.058

実験手法

X-RAY DIFFRACTION (2.2 Å)