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

被引：3

作者：

Bernini, Andrea ^{[1
]}

Spiga, Ottavia ^{[1
]}

Santucci, Annalisa ^{[1
,2
,3
]}

机构：

[1] Univ Siena, Dept Biotechnol Chem & Pharm, Siena, Italy

[2] Ctr Regionale Med Precis, Siena, Italy

[3] ARTES 4 0, Pontedera, Italy

来源：

CURRENT PROTEIN & PEPTIDE SCIENCE | 2023年 / 24卷 / 05期

关键词：

Alkaptonuria; protein structure; genotype-phenotype relationships; HGA; HGD; protein rescuers; NITISINONE; DIOXYGENASE; MUTATIONS; IDENTIFICATION; DIAGNOSIS; PATIENT; TRIAL; ACID;

D O I：

10.2174/1389203724666230307104135

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

收藏

页码：380 / 392

页数：13

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