NDLI: ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein-protein interactions with HPRT1.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Vasiliou, Vasilis Sandoval, Monica Backos, Donald S. Jackson, Brian C. Chen, Ying Reigan, Philip Lanaspa, Miguel A. Johnson, Richard J. Koppaka, Vindhya Thompson, David C.
Description	Country affiliation: United States Author Affiliation: Vasiliou V ( Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO 80045, USA. vasilis.vasiliou@ucdenver.edu)
Abstract	Gout, a common form of inflammatory arthritis, is strongly associated with elevated uric acid concentrations in the blood (hyperuricemia). A recent study in Icelanders identified a rare missense single nucleotide polymorphism (SNP) in the ALDH16A1 gene, ALDH16A12, to be associated with gout and serum uric acid levels. ALDH16A1 is a novel and rather unique member of the ALDH superfamily in relation to its gene and protein structures. ALDH16 genes are present in fish, amphibians, protista, bacteria but absent from archaea, fungi and plants. In most mammalian species, two ALDH16A1 spliced variants (ALDH16A1, long form and ALDH16A1_v2, short form) have been identified and both are expressed in HepG-2, HK-2 and HK-293 human cell lines. The ALDH16 proteins contain two ALDH domains (as opposed to one in the other members of the superfamily), four transmembrane and one coiled-coil domains. The active site of ALDH16 proteins from bacterial, frog and lower animals contain the catalytically important cysteine residue (Cys-302); this residue is absent from the mammalian and fish orthologs. Molecular modeling predicts that both the short and long forms of human ALDH16A1 protein would lack catalytic activity but may interact with the hypoxanthine-guanine phosphoribosyltransferase (HPRT1) protein, a key enzyme involved in uric acid metabolism and gout. Interestingly, such protein-protein interactions with HPRT1 are predicted to be impaired for the long or short forms of ALDH16A12. These results lead to the intriguing possibility that association between ALDH16A1 and HPRT1 may be required for optimal HPRT activity with disruption of this interaction possibly contributing to the hyperuricemia seen in ALDH16A1*2 carriers.
File Format	HTM / HTML
ISSN	00092797
e-ISSN	18727786
DOI	10.1016/j.cbi.2012.12.018
Journal	Chemico-Biological Interactions
Issue Number	1-3
Volume Number	202
Language	English
Publisher	Elsevier
Publisher Date	2013-02-25
Publisher Place	Ireland
Access Restriction	Open
Subject Keyword	Discipline Biochemistry Discipline Pharmacology Aldehyde Dehydrogenase Genetics Metabolism Gout Enzymology Hypoxanthine Phosphoribosyltransferase Amino Acid Sequence Animals Catalysis Catalytic Domain Cell Line Cell Line, Tumor Hek293 Cells Hep G2 Cells Hyperuricemia Models, Molecular Molecular Sequence Data Protein Interaction Domains And Motifs Rna Splice Sites Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Medicine Toxicology

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ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein–protein interactions with HPRT1

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ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein-protein interactions with HPRT1.