2can: Difference between revisions
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<StructureSection load='2can' size='340' side='right'caption='[[2can]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='2can' size='340' side='right'caption='[[2can]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2can]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2can]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CAN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CAN FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAN:CANALINE'>CAN</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2can FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2can OCA], [https://pdbe.org/2can PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2can RCSB], [https://www.ebi.ac.uk/pdbsum/2can PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2can ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2can FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2can OCA], [https://pdbe.org/2can PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2can RCSB], [https://www.ebi.ac.uk/pdbsum/2can PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2can ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
[https://www.uniprot.org/uniprot/OAT_HUMAN OAT_HUMAN] Defects in OAT are the cause of hyperornithinemia with gyrate atrophy of choroid and retina (HOGA) [MIM:[https://omim.org/entry/258870 258870]. HOGA is a slowly progressive blinding autosomal recessive disorder.<ref>PMID:3375240</ref> <ref>PMID:2793865</ref> <ref>PMID:1612597</ref> <ref>PMID:1737786</ref> <ref>PMID:7887415</ref> <ref>PMID:7668253</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/OAT_HUMAN OAT_HUMAN] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Brunger AT]] | |||
[[Category: Brunger | [[Category: Shah SA]] | ||
[[Category: Shah | [[Category: Shen BW]] | ||
[[Category: Shen | |||
Latest revision as of 09:42, 9 August 2023
HUMAN ORNITHINE AMINOTRANSFERASE COMPLEXED WITH L-CANALINEHUMAN ORNITHINE AMINOTRANSFERASE COMPLEXED WITH L-CANALINE
Structural highlights
DiseaseOAT_HUMAN Defects in OAT are the cause of hyperornithinemia with gyrate atrophy of choroid and retina (HOGA) [MIM:258870. HOGA is a slowly progressive blinding autosomal recessive disorder.[1] [2] [3] [4] [5] [6] FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBACKGROUND: Ornithine aminotransferase (OAT) is a 45 kDa pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes the conversion of L-ornithine and 2-oxoglutarate to glutamate-delta-semialdehyde and glutamic acid, respectively. In humans, loss of OAT function causes an accumulation of ornithine that results in gyrate atrophy of the choroid and retina, a disease that progressively leads to blindness. In an effort to learn more about the structural basis of this enzyme's function, we have determined the X-ray structures of OAT in complex with two enzyme-activated suicide substrates: L-canaline, an ornithine analog, and gabaculine, an irreversible inhibitor of several related aminotransferases. RESULTS: The structures of human OAT bound to the inhibitors gabaculine and L-canaline were solved to 2.3 A at 110K by difference Fourier techniques. Both inhibitors coordinate similarly in the active site, binding covalently to the PLP cofactor and causing a 20 degrees rotation in the cofactor tilt relative to the ligand-free form. Aromatic-aromatic interactions occur between the bound gabaculine molecule and active-site residues Tyr85 and Phe177, whereas Tyr55 and Arg180 provide specific contacts to the alpha-amino and carboxyl groups of L-canaline. CONCLUSIONS: The OAT-L-canaline complex structure implicates Tyr55 and Arg180 as the residues involved in coordinating with the natural substrate ornithine during normal enzyme turnover. This correlates well with two enzyme-inactivating point mutations associated with gyrate atrophy, Tyr55-->His and Arg180-->Thr. The OAT-gabaculine complex provides the first structural evidence that the potency of the inhibitor is due to energetically favourable aromatic interactions with residues in the active site. This aromatic-binding mode may be relevant to structure-based drug design efforts against other omega-aminotransferase targets, such as GABA aminotransferase. Human ornithine aminotransferase complexed with L-canaline and gabaculine: structural basis for substrate recognition.,Shah SA, Shen BW, Brunger AT Structure. 1997 Aug 15;5(8):1067-75. PMID:9309222[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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