2can
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2can.gif|left|200px]] | + | [[Image:2can.gif|left|200px]] |
| - | + | ||
| - | '''HUMAN ORNITHINE AMINOTRANSFERASE COMPLEXED WITH L-CANALINE''' | + | {{Structure |
| + | |PDB= 2can |SIZE=350|CAPTION= <scene name='initialview01'>2can</scene>, resolution 2.30Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CAN:CANALINE'>CAN</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Ornithine_aminotransferase Ornithine aminotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.13 2.6.1.13] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''HUMAN ORNITHINE AMINOTRANSFERASE COMPLEXED WITH L-CANALINE''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2CAN is a [ | + | 2CAN 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=2CAN OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/9309222 9309222] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Ornithine aminotransferase]] | [[Category: Ornithine aminotransferase]] | ||
| Line 26: | Line 35: | ||
[[Category: urea cycle]] | [[Category: urea cycle]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:13:06 2008'' |
Revision as of 14:13, 20 March 2008
| |||||||
| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Ornithine aminotransferase, with EC number 2.6.1.13 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN ORNITHINE AMINOTRANSFERASE COMPLEXED WITH L-CANALINE
Contents |
Overview
BACKGROUND: 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.
Disease
Known disease associated with this structure: Gyrate atrophy of choroid and retina with ornithinemia, B6 responsive or unresponsive OMIM:[258870]
About this Structure
2CAN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Mar 20 16:13:06 2008
