Human antiquitin: Structural and functional studies
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AbstractAntiquitin (ALDH7) is a member of the aldehyde dehydrogenase superfamily which oxidizes various aldehydes to form the corresponding carboxylic acids. Human antiquitin (ALDH7A1) is believed to play a role in detoxification, osmoregulation and more specifically, in lysine metabolism in which alpha-aminoadipic semialdehyde is identified as the specific, physiological substrate of the enzyme. In the present study, the structural basis for the substrate specificity was studied by site-directed mutagenesis. Kinetic analysis on wild-type human antiquitin and its mutants E121A and R301A demonstrated the importance of Glul 21 and Arg301 in the binding as well as the turnover of alpha-aminoadipic semialdehyde. On the functional aspect, in addition to the already diversified physiological functions of antiquitin, the recent demonstration of its presence in the nucleus suggests that it may also play a role in cell growth and cell cycle progression. In this investigation, the expression level of antiquitin was monitored in synchronized WRL68 and HEK293 cell culture systems. It was found that the protein was up-regulated during G(1)-S phase transition. Immunofluorescence staining of the synchronized cells demonstrated an increased expression and accumulation of antiquitin in the nucleus during the G(1)-S phase transition. Knockdown of antiquitin using shRNA transfection also resulted in changes in the levels of several key cell cycle-regulating proteins. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
All Author(s) ListChan CL, Wong JWY, Wong CP, Chan MKL, Fong WP
Journal nameChemico-Biological Interactions
Year2011
Month5
Day30
Volume Number191
Issue Number1-3
PublisherElsevier
Pages165 - 170
ISSN0009-2797
eISSN1872-7786
LanguagesEnglish-United Kingdom
KeywordsAldehyde dehydrogenase; Antiquitin; Cell cycle; Site-directed mutagenesis
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY; Toxicology; TOXICOLOGY

Last updated on 2020-20-11 at 00:22