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  • 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.
  • 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. (en)
Title
  • Random mutagenesis of human serine racemase reveals residues important for the enzymatic activity
  • Random mutagenesis of human serine racemase reveals residues important for the enzymatic activity (en)
skos:prefLabel
  • Random mutagenesis of human serine racemase reveals residues important for the enzymatic activity
  • Random mutagenesis of human serine racemase reveals residues important for the enzymatic activity (en)
skos:notation
  • RIV/61388963:_____/10:00343324!RIV11-MSM-61388963
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(1M0508), Z(AV0Z40550506)
http://linked.open...iv/cisloPeriodika
  • 1
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 283875
http://linked.open...ai/riv/idVysledku
  • RIV/61388963:_____/10:00343324
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • D-serine; serine racemase; random mutagenesis (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • CZ - Česká republika
http://linked.open...ontrolniKodProRIV
  • [B22330C2580C]
http://linked.open...i/riv/nazevZdroje
  • Collection of Czechoslovak Chemical Communications
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
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http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 75
http://linked.open...iv/tvurceVysledku
  • Konvalinka, Jan
  • Hoffman, Hillary Elizabeth
  • Jirásková, Jana
  • Zvelebil, M.
http://linked.open...ain/vavai/riv/wos
  • 000274668100004
http://linked.open...n/vavai/riv/zamer
issn
  • 0010-0765
number of pages
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