OAT + PLP, Human
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / QuickGO|
|Locus||Chr. 10 q26|
The OAT involved in the ultimate formation of the non-essential amino acid proline from the amino acid ornithine. Ornithine aminotransferase forms the initial intermediate in this process. It catalyzes the reverse reaction as well, and is therefore essential in creating ornithine from the starting substrate proline.
The OAT gene encodes for a protein that is approximately 46 kDa in size. The OAT protein is expressed primarily in the liver and the kidney but also in the brain and the retina. The OAT protein is localized to the mitochondrion within the cells where it is expressed.
The structure of the OAT protein has been resolved using X-ray crystallography and shows similarity to other subgroup 2 aminotransferases such as dialkyglucine decarboxylatse. The OAT protein functions as a dimer and each monomer consists of a large domain, which contributes most to subunit interface, and a C-terminal small domain, and an N-terminal region containing a helix, loop, and three-stranded beta-meander. In the central large domain is a seven-stranded beta-sheet covered by eight helices. The co-factor of the OAT protein (pyridoxal-5'-phosphate) binds to OAT through a Schiff base at the lysine 292 position situated between two of the seven-stranded beta-sheet. Three amino acids (R 180, E 235, and R413) are thought to be involved in substrate binding at the active site.
Ornithine aminotransferase catalyzes the transfer of the delta-amino group from L-ornithine
- L-ornithine + a 2-oxo acid = L-glutamate 5-semialdehyde + an L-amino acid
Mutations in the OAT gene can lead to malfunctioning proteins, including both point mutations that abolish catalytic activities, large frame-shift mutations, as well as mutated proteins that are not properly targeted to the mitochondrion where its normal functionality occurs. In the latter, abnormality of mitochondrial import causes ectopic accumulation of the OAT protein in the cytosol followed by rapid degradation by proteolysis. Deficiency of OAT activities causes ornithine aminotransferase deficiency, also known as gyrate atrophy of choroid and retina.
- Rao GN, Cotlier E (1984). "Ornithine delta-aminotransferase activity in retina and other tissues". Neurochem. Res. 9 (4): 555–62. doi:10.1007/bf00964382. PMID 6462326. S2CID 19775002.
- Kobayashi T, Ogawa H, Kasahara M, Shiozawa Z, Matsuzawa T (1995). "A single amino acid substitution within the mature sequence of ornithine aminotransferase obstructs mitochondrial entry of the precursor". Am. J. Hum. Genet. 57 (2): 284–91. PMC 1801533. PMID 7668253.
- Shen BW, Hennig M, Hohenester E, Jansonius JN, Schirmer T (1998). "Crystal structure of human recombinant ornithine aminotransferase". J. Mol. Biol. 277 (1): 81–102. doi:10.1006/jmbi.1997.1583. PMID 9514741.
- "Gyrate atrophy of the choroid and retina". National Institutes of Health. Retrieved 2012-08-23.
- Kim SJ, Lim DH, Kim JH, Kang SW (2013). "Gyrate atrophy of the choroid and retina diagnosed by ornithine-δ-aminotransferase gene analysis: a case report". Korean J Ophthalmol. 27 (5): 388–91. doi:10.3341/kjo.2013.27.5.388. PMC 3782588. PMID 24082780.
- Katagiri S, Gekka T, Hayashi T, Ida H, Ohashi T, Eto Y, Tsuneoka H (2014). "OAT mutations and clinical features in two Japanese brothers with gyrate atrophy of the choroid and retina". Doc Ophthalmol. 128 (2): 137–48. doi:10.1007/s10633-014-9426-1. PMID 24429551. S2CID 713618.
- Doimo M, Desbats MA, Baldoin MC, Lenzini E, Basso G, Murphy E, Graziano C, Seri M, Burlina A, Sartori G, Trevisson E, Salviati L (2013). "Functional analysis of missense mutations of OAT, causing gyrate atrophy of choroid and retina". Hum. Mutat. 34 (1): 229–36. doi:10.1002/humu.22233. PMID 23076989. S2CID 205921336.