2abj

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spinqualitylabelsall models 2abj, resolution 2.200Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Hyperleucinemia-isoleucinemia or hypervalinemia (1) OMIM:[113520]

About this Structure

2ABJ is a Single protein structure of sequence from Homo sapiens with CBC and PLP as ligands. Active as Branched-chain-amino-acid transaminase, with EC number 2.6.1.42 Full crystallographic information is available from OCA.

Reference

The design and synthesis of human branched-chain amino acid aminotransferase inhibitors for treatment of neurodegenerative diseases., Hu LY, Boxer PA, Kesten SR, Lei HJ, Wustrow DJ, Moreland DW, Zhang L, Ahn K, Ryder TR, Liu X, Rubin JR, Fahnoe K, Carroll RT, Dutta S, Fahnoe DC, Probert AW, Roof RL, Rafferty MF, Kostlan CR, Scholten JD, Hood M, Ren XD, Schielke GP, Su TZ, Taylor CP, Mistry A, McConnell P, Hasemann C, Ohren J, Bioorg Med Chem Lett. 2006 May 1;16(9):2337-40. Epub 2005 Sep 6. PMID:16143519

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