1ohy: Difference between revisions
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|PDB= 1ohy |SIZE=350|CAPTION= <scene name='initialview01'>1ohy</scene>, resolution 2.80Å | |PDB= 1ohy |SIZE=350|CAPTION= <scene name='initialview01'>1ohy</scene>, resolution 2.80Å | ||
|SITE= <scene name='pdbsite=AC1:S+Binding+Site+For+Chain+D'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:S+Binding+Site+For+Chain+D'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> | |LIGAND= <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GEG:(4E)-4-AMINOHEX-4-ENOIC+ACID'>GEG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=S:SULFUR+ATOM'>S</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/4-aminobutyrate_transaminase 4-aminobutyrate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.19 2.6.1.19] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/4-aminobutyrate_transaminase 4-aminobutyrate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.19 2.6.1.19] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ohy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ohy OCA], [http://www.ebi.ac.uk/pdbsum/1ohy PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ohy RCSB]</span> | |||
}} | }} | ||
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[[Category: Schirmer, T.]] | [[Category: Schirmer, T.]] | ||
[[Category: Storici, P.]] | [[Category: Storici, P.]] | ||
[[Category: 4-aminobutyric acid]] | [[Category: 4-aminobutyric acid]] | ||
[[Category: aminotransferase]] | [[Category: aminotransferase]] | ||
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[[Category: vigabatrin pyridoxal phosphate]] | [[Category: vigabatrin pyridoxal phosphate]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:45:36 2008'' | ||
Revision as of 19:45, 30 March 2008
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| 1ohy, resolution 2.80Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sites: | AC1 | ||||||||||||
| Ligands: | FE, GEG, PLP, S | ||||||||||||
| Activity: | 4-aminobutyrate transaminase, with EC number 2.6.1.19 | ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
4-AMINOBUTYRATE-AMINOTRANSFERASE INACTIVATED BY GAMMA-ETHYNYL GABA
Overview
Gamma-aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate-dependent enzyme responsible for the degradation of the inhibitory neurotransmitter GABA. GABA-AT is a validated target for antiepilepsy drugs because its selective inhibition raises GABA concentrations in brain. The antiepilepsy drug, gamma-vinyl-GABA (vigabatrin) has been investigated in the past by various biochemical methods and resulted in several proposals for its mechanisms of inactivation. In this study we solved and compared the crystal structures of pig liver GABA-AT in its native form (to 2.3-A resolution) and in complex with vigabatrin as well as with the close analogue gamma-ethynyl-GABA (to 2.3 and 2.8 A, respectively). Both inactivators form a covalent ternary adduct with the active site Lys-329 and the pyridoxal 5'-phosphate (PLP) cofactor. The crystal structures provide direct support for specific inactivation mechanisms proposed earlier on the basis of radio-labeling experiments. The reactivity of GABA-AT crystals with the two GABA analogues was also investigated by polarized absorption microspectrophotometry. The spectral data are discussed in relation to the proposed mechanism. Intriguingly, all three structures revealed a [2Fe-2S] cluster of yet unknown function at the center of the dimeric molecule in the vicinity of the PLP cofactors.
About this Structure
1OHY is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
Reference
Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin., Storici P, De Biase D, Bossa F, Bruno S, Mozzarelli A, Peneff C, Silverman RB, Schirmer T, J Biol Chem. 2004 Jan 2;279(1):363-73. Epub 2003 Oct 8. PMID:14534310
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