Publications

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

Authors:
Montioli, Riccardo; Zamparelli, Carlotta; Borri Voltattorni, Carla; Cellini, Barbara
Title:
Oligomeric state and thermal stability of apo- and holo- human ornithine δ-aminotransferase
Year:
2017
Type of item:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Language:
Inglese
Format:
A Stampa
Referee:
Name of journal:
PROTEIN JOURNAL
ISSN of journal:
1572-3887
N° Volume:
36
Number or Folder:
3
Page numbers:
174-185
Keyword:
coenzyme; interface contacts; protein stability; pyridoxal 5′-phosphate; quaternary structure; tetramer–dimer equilibrium
Short description of contents:
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.
Web page:
https://doi.org/10.1007/s10930-017-9710-5
Product ID:
97619
Handle IRIS:
11562/963148
Last Modified:
November 14, 2022
Bibliographic citation:
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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