Pubblicazioni

Oligomeric state and thermal stability of apo- and holo- human ornithine δ-aminotransferase  (2017)

Autori:
Montioli, Riccardo; Zamparelli, Carlotta; Borri Voltattorni, Carla; Cellini, Barbara
Titolo:
Oligomeric state and thermal stability of apo- and holo- human ornithine δ-aminotransferase
Anno:
2017
Tipologia prodotto:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Lingua:
Inglese
Formato:
A Stampa
Referee:
Nome rivista:
PROTEIN JOURNAL
ISSN Rivista:
1572-3887
N° Volume:
36
Numero o Fascicolo:
3
Intervallo pagine:
174-185
Parole chiave:
coenzyme; interface contacts; protein stability; pyridoxal 5′-phosphate; quaternary structure; tetramer–dimer equilibrium
Breve descrizione dei contenuti:
Human ornithine δ-aminotransferase (hOAT) (EC 2.6.1.13) is a mitochondrial pyridoxal 5'-phosphate (PLP)-dependent aminotransferase whose deficit is associated with gyrate atrophy, a rare autosomal recessive disorder causing progressive blindness and chorioretinal degeneration. Here, both the apo- and holo-form of recombinant hOAT were characterized by means of spectroscopic, kinetic, chromatographic and computational techniques. The results indicate that apo and holo-hOAT (a) show a similar tertiary structure, even if apo displays a more pronounced exposure of hydrophobic patches, (b) exhibit a tetrameric structure with a tetramer-dimer equilibrium dissociation constant about fivefold higher for the apoform with respect to the holoform, and (c) have apparent Tm values of 46 and 67 °C, respectively. Moreover, unlike holo-hOAT, apo-hOAT is prone to unfolding and aggregation under physiological conditions. We also identified Arg217 as an important hot-spot at the dimer-dimer interface of hOAT and demonstrated that the artificial dimeric variant R217A exhibits spectroscopic properties, Tm values and catalytic features similar to those of the tetrameric species. This finding indicates that the catalytic unit of hOAT is the dimer. However, under physiological conditions the apo-tetramer is slightly less prone to unfolding and aggregation than the apo-dimer. The possible implications of the data for the intracellular stability and regulation of hOAT are discussed.
Pagina Web:
https://doi.org/10.1007/s10930-017-9710-5
Id prodotto:
97619
Handle IRIS:
11562/963148
ultima modifica:
14 novembre 2022
Citazione bibliografica:
Montioli, Riccardo; Zamparelli, Carlotta; Borri Voltattorni, Carla; Cellini, Barbara, Oligomeric state and thermal stability of apo- and holo- human ornithine δ-aminotransferase «PROTEIN JOURNAL» , vol. 36 , n. 32017pp. 174-185

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