2abj

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[[Image:2abj.gif|left|200px]]<br /><applet load="2abj" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2abj.gif|left|200px]]
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caption="2abj, resolution 2.200&Aring;" />
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'''Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.'''<br />
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{{Structure
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|PDB= 2abj |SIZE=350|CAPTION= <scene name='initialview01'>2abj</scene>, resolution 2.200&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=CBC:N'-(5-CHLOROBENZOFURAN-2-CARBONYL)-2-(TRIFLUOROMETHYL)BENZENESULFONOHYDRAZIDE'>CBC</scene> and <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene>
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|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]
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|GENE= BCAT1, BCT1, ECA39 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Crystal structure of human branched chain amino acid transaminase in a complex with an inhibitor, C16H10N2O4F3SCl, and pyridoxal 5' phosphate.'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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].
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2ABJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ABJ OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16143519 16143519]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/16143519 16143519]
[[Category: Branched-chain-amino-acid transaminase]]
[[Category: Branched-chain-amino-acid transaminase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: pyridoxal-phosphate-dependent aminotransferase]]
[[Category: pyridoxal-phosphate-dependent aminotransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:25:47 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:47:46 2008''

Revision as of 13:47, 20 March 2008

Image:2abj.gif


PDB ID 2abj

Drag the structure with the mouse to rotate
, resolution 2.200Å
Ligands: and
Gene: BCAT1, BCT1, ECA39 (Homo sapiens)
Activity: Branched-chain-amino-acid transaminase, with EC number 2.6.1.42
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.


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. 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 Mar 20 15:47:46 2008

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