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Random mutagenesis of human serine racemase reveals residues important for the enzymatic activity

SYSNO ASEP	0343324
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Random mutagenesis of human serine racemase reveals residues important for the enzymatic activity
Author(s)	Hoffman, Hillary Elizabeth (UOCHB-X) Jirásková, Jana (UOCHB-X) Zvelebil, M. (GB) Konvalinka, Jan (UOCHB-X)_{RID, ORCID}
Number of authors	4
Source Title	Collection of Czechoslovak Chemical Communications. - : Ústav organické chemie a biochemie AV ČR, v. v. i. - ISSN 0010-0765 Roč. 75, č. 1 (2010), s. 59-79
Number of pages	21 s.
Language	eng - English
Country	CZ - Czech Republic
Keywords	D-serine ; serine racemase ; random mutagenesis
Subject RIV	CE - Biochemistry
R&D Projects	1M0508 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
CEZ	AV0Z40550506 - UOCHB-X (2005-2011)
UT WOS	000274668100004
DOI	10.1135/cccc2010003
Annotation	Human serine racemase (hSR) is a cytosolic pyridoxal-5′-phosphate dependent enzyme responsible for production of D-serine in the central nervous system. D-Serine acts as an endogenous coagonist of N-methyl-D-aspartate receptor ion channels. Increased levels of D-serine have been linked to amyotrophic lateral sclerosis and Alzheimer’s disease.Here, we present a strategy for the generation and screening of random hSR mutants. From a library of randomly mutated hSR variants, twenty-seven soluble mutants were selected, expressed, and evaluated for enzymatic activity. Taking three carefully characterized mutants as an example, we show how this strategy can be used to pinpoint structurally and functionally important residues. In particular, we identify S84 and P111 as residues crucial for hSR activity and C217 and K221 as residues important for binding of the Mg2+ cofactor.
Workplace	Institute of Organic Chemistry and Biochemistry
Contact	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Year of Publishing	2011

Number of the records: 1