{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:12:20Z","timestamp":1787944340312,"version":"build-2784847793"},"reference-count":67,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Human ornithine aminotransferase (hOAT) is a mitochondrial matrix pyridoxal\u20105\u2032\u2010phosphate enzyme (PLP) that catalyzes the reversible transfer of the \u03b4\u2010amino group of L\u2010ornithine (L\u2010Orn) to \u03b1\u2010ketoglutarate (\u03b1\u2010KG) yielding glutamate\u20105\u2010semialdehyde (GSA) and glutamate. GSA is prone to cyclize to \u03941\u2010pyrroline\u20105\u2010carboxylate. Human OAT holds significant clinical and scientific interest because (i) its dysfunction causes gyrate atrophy (GA) of the choroid and retina, a rare autosomal recessive disease, and (ii) it is recognized as a potential target for chemotherapeutic drug development, being overexpressed in some types of cancer. Here, we review the kinetic and structural features of the enzyme, as well as the mechanistic aspects of hOAT inhibition. Moreover, we focus our attention on the characterization of the structural and functional properties of the artificial variants and of those associated with GA. Considering that great progress toward the characterization of the pathogenic variants has been reached in the last few years, we summarize here, by revisiting the data available on the hOAT and its variants as purified recombinant form, the current understanding of (i) the molecular defect(s) of studied disease\u2010causing mutations and (ii) the residues (particularly, active site residues critical for dictating the reaction specificity) and\/or regions of the enzyme crucial for its folding and\/or catalytic properties.<\/jats:p>","DOI":"10.1002\/prot.70134","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T01:54:52Z","timestamp":1774576492000},"page":"1431-1441","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Current Insight into Human Ornithine Aminotransferase: A Review"],"prefix":"10.1002","volume":"94","author":[{"given":"Fulvio","family":"Floriani","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Biomedicine, and Movement Sciences, Biological Chemistry Section University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Borri Voltattorni","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine, and Movement Sciences, Biological Chemistry Section University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Montioli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine, and Movement Sciences, Biological Chemistry Section University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology6010018"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-013-1608-8"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.074021"},{"key":"e_1_2_11_5_1","first-page":"129","article-title":"The Molecular Evolution of Pyridoxal\u20105\u2032\u2010Phosphate\u2010Dependent Enzymes","volume":"74","author":"Mehta P. 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