Structure-Function Relationship of Homogentisate 1,2-dioxygenase: Understanding the Genotype-Phenotype Correlations in the Rare Genetic Disease Alkaptonuria.
Alkaptonuria
HGA
HGD
genotype-phenotype relationships
protein rescuers
protein structure
Journal
Current protein & peptide science
ISSN: 1875-5550
Titre abrégé: Curr Protein Pept Sci
Pays: United Arab Emirates
ID NLM: 100960529
Informations de publication
Date de publication:
2023
2023
Historique:
received:
02
08
2022
revised:
16
01
2023
accepted:
26
01
2023
medline:
6
7
2023
pubmed:
8
3
2023
entrez:
7
3
2023
Statut:
ppublish
Résumé
Alkaptonuria (AKU), a rare genetic disorder, is characterized by the accumulation of homogentisic acid (HGA) in organs, which occurs because the homogentisate 1,2-dioxygenase (HGD) enzyme is not functional due to gene variants. Over time, HGA oxidation and accumulation cause the formation of the ochronotic pigment, a deposit that provokes tissue degeneration and organ malfunction. Here, we report a comprehensive review of the variants so far reported, the structural studies on the molecular consequences of protein stability and interaction, and molecular simulations for pharmacological chaperones as protein rescuers. Moreover, evidence accumulated so far in alkaptonuria research will be re-proposed as the bases for a precision medicine approach in a rare disease.
Identifiants
pubmed: 36880186
pii: CPPS-EPUB-130031
doi: 10.2174/1389203724666230307104135
doi:
Substances chimiques
Dioxygenases
EC 1.13.11.-
Homogentisate 1,2-Dioxygenase
EC 1.13.11.5
Homogentisic Acid
NP8UE6VF08
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
380-392Subventions
Organisme : Regione Toscana
ID : D78D20000870002.
Informations de copyright
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