2abj
From Proteopedia
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|PDB= 2abj |SIZE=350|CAPTION= <scene name='initialview01'>2abj</scene>, resolution 2.200Å | |PDB= 2abj |SIZE=350|CAPTION= <scene name='initialview01'>2abj</scene>, resolution 2.200Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CBC:N'-(5-CHLOROBENZOFURAN-2-CARBONYL)-2-(TRIFLUOROMETHYL)BENZENESULFONOHYDRAZIDE'>CBC</scene> | + | |LIGAND= <scene name='pdbligand=CBC:N'-(5-CHLOROBENZOFURAN-2-CARBONYL)-2-(TRIFLUOROMETHYL)BENZENESULFONOHYDRAZIDE'>CBC</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Branched-chain-amino-acid_transaminase Branched-chain-amino-acid transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.42 2.6.1.42] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Branched-chain-amino-acid_transaminase Branched-chain-amino-acid transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.42 2.6.1.42] </span> |
|GENE= BCAT1, BCT1, ECA39 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= BCAT1, BCT1, ECA39 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2abj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2abj OCA], [http://www.ebi.ac.uk/pdbsum/2abj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2abj RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=113520 113520]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Rubin, J R.]] | [[Category: Rubin, J R.]] | ||
[[Category: Scholten, J D.]] | [[Category: Scholten, J D.]] | ||
| - | [[Category: CBC]] | ||
| - | [[Category: PLP]] | ||
[[Category: branched-chain-amino-acid aminotransferase]] | [[Category: branched-chain-amino-acid aminotransferase]] | ||
[[Category: cytosolic]] | [[Category: cytosolic]] | ||
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[[Category: pyridoxal-phosphate-dependent aminotransferase]] | [[Category: pyridoxal-phosphate-dependent aminotransferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:50:32 2008'' |
Revision as of 22:50, 30 March 2008
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| , resolution 2.200Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | BCAT1, BCT1, ECA39 (Homo sapiens) | ||||||
| Activity: | Branched-chain-amino-acid transaminase, with EC number 2.6.1.42 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.
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.
About this Structure
2ABJ is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Mon Mar 31 01:50:32 2008
Categories: Branched-chain-amino-acid transaminase | Homo sapiens | Single protein | Hasemann, C H. | Hu, H L. | McConnell, P C. | Mistry, A. | Moreland, D W. | Mueller, W T. | Ohren, J F. | Rubin, J R. | Scholten, J D. | Branched-chain-amino-acid aminotransferase | Cytosolic | Inhibitor-bound | Plp-lys220 schiff base | Pyridoxal-phosphate-dependent aminotransferase
