Pubblicazioni

Autori:

Floriani, Fulvio; Borri Voltattorni, Carla; Cellini, Barbara; Montioli, Riccardo

Titolo:

Biochemical and bioinformatic studies of mutations of residues at the monomer-monomer interface of human ornithine aminotransferase leading to gyrate atrophy of choroid and retina

Anno:

2023

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

Elettronico

Referee:

Sì

Nome rivista:

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ISSN Rivista:

1422-0067

N° Volume:

24

Numero o Fascicolo:

4

Intervallo pagine:

1-17

Parole chiave:

gyrate atrophy of choroid and retina; interface mutations; ornithine aminotransferase; pathogenic variants; pyridoxal 5′-phosphate

Breve descrizione dei contenuti:

Deficit of human ornithine aminotransferase (hOAT), a mitochondrial tetrameric pyridoxal-5'-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-monomer 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 ΔΔG values of monomer-monomer binding for the variants, suggest that the proper monomer-monomer 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.

Pagina Web:

https://doi.org/10.3390/ijms24043369

Id prodotto:

132757

Handle IRIS:

11562/1088131

ultima modifica:

28 marzo 2023

Citazione bibliografica:

Floriani, Fulvio; Borri Voltattorni, Carla; Cellini, Barbara; Montioli, Riccardo, Biochemical and bioinformatic studies of mutations of residues at the monomer-monomer interface of human ornithine aminotransferase leading to gyrate atrophy of choroid and retina «INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES» , vol. 24 , n. 4 , 2023 , pp. 1-17

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo