2ABJ

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

Summary for 2ABJ

• Entry DOI: 10.2210/pdb2abj/pdb
• Descriptor: Branched-chain-amino-acid aminotransferase, cytosolic, N'-(5-CHLOROBENZOFURAN-2-CARBONYL)-2-(TRIFLUOROMETHYL)BENZENESULFONOHYDRAZIDE, PYRIDOXAL-5'-PHOSPHATE, ... (4 entities in total)
• Functional Keywords: branched-chain-amino-acid aminotransferase, cytosolic, pyridoxal-phosphate-dependent aminotransferase, plp-lys220 schiff base, inhibitor-bound, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P54687
• Total number of polymer chains: 4
• Total formula weight: 167079.43

Authors

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. (deposition date: 2005-07-15, release date: 2006-06-27, Last modification date: 2017-10-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)