Počet záznamů: 1

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

  1. 1.
    0343324 - UOCHB-X 2011 RIV CZ eng J - Článek v odborném periodiku
    Hoffman, Hillary Elizabeth - Jirásková, Jana - Zvelebil, M. - Konvalinka, Jan
    Random mutagenesis of human serine racemase reveals residues important for the enzymatic activity.
    Collection of Czechoslovak Chemical Communications. Roč. 75, č. 1 (2010), s. 59-79 ISSN 0010-0765
    Grant CEP: GA MŠk 1M0508
    Výzkumný záměr: CEZ:AV0Z40550506
    Klíčová slova: D-serine * serine racemase * random mutagenesis
    Kód oboru RIV: CE - Biochemie
    Impakt faktor: 0.853, rok: 2010

    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.
    Trvalý link: http://hdl.handle.net/11104/0185830