The Role for Glutamic Acid at Position 196 in Human Hypoxanthine Phosphoribosyltransferase (HPRT) as Investigated Using Site-Directed Mutagenesis

Autor:	A E-Wan, L Sirisatean, W Keawwijit, Bhutorn Canyuk, Pimpimon Tansakul, Teerapat Nualnoi, C Tanthana
Rok vydání:	2008
Předmět:	Hypoxanthine Phosphoribosyltransferase Stereochemistry Dimer Guanosine Monophosphate Glutamic Acid Biochemistry Catalysis chemistry.chemical_compound Protein structure Valine Genetics Humans Protein Structure Quaternary Site-directed mutagenesis Sepharose Mutagenesis General Medicine Recombinant Proteins Kinetics chemistry Catalytic cycle Hypoxanthine-guanine phosphoribosyltransferase Mutagenesis Site-Directed Molecular Medicine Mutant Proteins Dimerization
Zdroj:	Nucleosides, Nucleotides and Nucleic Acids. 27:894-899
ISSN:	1532-2335 1525-7770
DOI:	10.1080/15257770802146593
Popis:	The crystal structure of human HPRT reveals the involvement of E196 side chain at the A-B dimer interface. Interference by valine substitution at this position (E196V), as identified in patients with Lesch-Nyhan disease, nearly abolishes enzymatic activity. Kinetic analysis of the active mutants (E196A, E196D, E196Q, and E196R) suggests that interaction between K68 and E196 side chains contributes to stabilization of cis-configuration during the catalytic cycle. The study also provides further insight into the role of A-B dimer interactions relating to K68 in the regulation of cis-trans isomerization that potentially governs the rate-limiting steps in the HPRT reaction.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2edeedec3147fa3d9096d4c12d0198f https://doi.org/10.1080/15257770802146593 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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