2abj
From Proteopedia
(New page: 200px<br /> <applet load="2abj" size="450" color="white" frame="true" align="right" spinBox="true" caption="2abj, resolution 2.200Å" /> '''Crystal structure ...) |
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| - | [[Image:2abj.gif|left|200px]]<br /> | + | [[Image:2abj.gif|left|200px]]<br /><applet load="2abj" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2abj" size=" | + | |
caption="2abj, resolution 2.200Å" /> | caption="2abj, resolution 2.200Å" /> | ||
'''Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.'''<br /> | '''Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The inhibition of the cytosolic isoenzyme BCAT that is expressed | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2ABJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CBC and PLP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 2ABJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CBC:'>CBC</scene> and <scene name='pdbligand=PLP:'>PLP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ABJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Hasemann, C | + | [[Category: Hasemann, C H.]] |
| - | [[Category: Hu, H | + | [[Category: Hu, H L.]] |
| - | [[Category: McConnell, P | + | [[Category: McConnell, P C.]] |
[[Category: Mistry, A.]] | [[Category: Mistry, A.]] | ||
| - | [[Category: Moreland, D | + | [[Category: Moreland, D W.]] |
| - | [[Category: Mueller, W | + | [[Category: Mueller, W T.]] |
| - | [[Category: Ohren, J | + | [[Category: Ohren, J F.]] |
| - | [[Category: Rubin, J | + | [[Category: Rubin, J R.]] |
| - | [[Category: Scholten, J | + | [[Category: Scholten, J D.]] |
[[Category: CBC]] | [[Category: CBC]] | ||
[[Category: PLP]] | [[Category: PLP]] | ||
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[[Category: pyridoxal-phosphate-dependent aminotransferase]] | [[Category: pyridoxal-phosphate-dependent aminotransferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:25:47 2008'' |
Revision as of 14:25, 21 February 2008
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Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.
Contents |
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 and 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
Page seeded by OCA on Thu Feb 21 16:25:47 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. | CBC | PLP | Branched-chain-amino-acid aminotransferase | Cytosolic | Inhibitor-bound | Plp-lys220 schiff base | Pyridoxal-phosphate-dependent aminotransferase
