Structure-Function Relationship of Homogentisate 1,2-dioxygenase:
Understanding the Genotype-Phenotype Correlations in the Rare Genetic
Disease Alkaptonuria

Andrea      Bernini; Ottavia      Spiga; Annalisa      Santucci
doi:10.2174/1389203724666230307104135
Abstract

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.
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DOI https://dx.doi.org/10.2174/1389203724666230307104135	Print ISSN 1389-2037
Publisher Name Bentham Science Publisher	Online ISSN 1875-5550
Current Protein & Peptide Science

Structure-Function Relationship of Homogentisate 1,2-dioxygenase: Understanding the Genotype-Phenotype Correlations in the Rare Genetic Disease Alkaptonuria

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