{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T11:43:54Z","timestamp":1774611834987,"version":"3.50.1"},"reference-count":21,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007052","name":"University of Verona","doi-asserted-by":"publisher","award":["FUR2022"],"award-info":[{"award-number":["FUR2022"]}],"id":[{"id":"10.13039\/501100007052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Deficit of human ornithine aminotransferase (hOAT), a mitochondrial tetrameric pyridoxal-5\u2032-phosphate (PLP) enzyme, leads to gyrate atrophy of the choroid and retina (GA). Although 70 pathogenic mutations have been identified, only few enzymatic phenotypes are known. Here, we report biochemical and bioinformatic analyses of the G51D, G121D, R154L, Y158S, T181M, and P199Q pathogenic variants involving residues located at the monomer\u2013monomer interface. All mutations cause a shift toward a dimeric structure, and changes in tertiary structure, thermal stability, and PLP microenvironment. The impact on these features is less pronounced for the mutations of Gly51 and Gly121 mapping to the N-terminal segment of the enzyme than those of Arg154, Tyr158, Thr181, and Pro199 belonging to the large domain. These data, together with the predicted \u0394\u0394G values of monomer\u2013monomer binding for the variants, suggest that the proper monomer\u2013monomer interactions seem to be correlated with the thermal stability, the PLP binding site and the tetrameric structure of hOAT. The different impact of these mutations on the catalytic activity was also reported and discussed on the basis of the computational information. Together, these results allow the identification of the molecular defects of these variants, thus extending the knowledge of enzymatic phenotypes of GA patients.<\/jats:p>","DOI":"10.3390\/ijms24043369","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T04:21:59Z","timestamp":1675830119000},"page":"3369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Biochemical and Bioinformatic Studies of Mutations of Residues at the Monomer\u2013Monomer Interface of Human Ornithine Aminotransferase Leading to Gyrate Atrophy of Choroid and Retina"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6018-7119","authenticated-orcid":false,"given":"Fulvio","family":"Floriani","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biological Chemistry, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Borri Voltattorni","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biological Chemistry, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5221-9288","authenticated-orcid":false,"given":"Barbara","family":"Cellini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Montioli","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biological Chemistry, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1073\/pnas.83.5.1203","article-title":"Molecular cloning of human ornithine aminotransferase mRNA","volume":"83","author":"Inana","year":"1986","journal-title":"Proc. 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