About: Kinetic and structural characterization of an alternatively spliced variant of human mitochondrial 5'(3')-deoxyribonucleotidase     Goto   Sponge   NotDistinct   Permalink

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  • Abstract Human mitochondrial 5'(3')-deoxyribonucleotidase (mdN) catalyzes dephosphorylation of nucleoside monophosphates, and thus helps maintain homeostasis of deoxynucleosides required for mitochondrial DNA synthesis. Mature mdN is a 23-kDa dimeric protein with highest expression levels in the heart, brain and skeletal muscle. We have identified an alternative splice variant of the mdN gene containing an 18-nucleotide insertion encoding 6 amino acids (GKWPAT) at the 3'-end of the penultimate exon 4. We recombinantly expressed this enzyme variant and characterized its biochemical and kinetic properties as well as its three-dimensional structure. Our high-resolution (1.27 Å) crystal structure revealed that the insertion forms a loop located in the vicinity of the active site pocket and affects enzyme kinetic parameters as well as protein thermal stability.
  • Abstract Human mitochondrial 5'(3')-deoxyribonucleotidase (mdN) catalyzes dephosphorylation of nucleoside monophosphates, and thus helps maintain homeostasis of deoxynucleosides required for mitochondrial DNA synthesis. Mature mdN is a 23-kDa dimeric protein with highest expression levels in the heart, brain and skeletal muscle. We have identified an alternative splice variant of the mdN gene containing an 18-nucleotide insertion encoding 6 amino acids (GKWPAT) at the 3'-end of the penultimate exon 4. We recombinantly expressed this enzyme variant and characterized its biochemical and kinetic properties as well as its three-dimensional structure. Our high-resolution (1.27 Å) crystal structure revealed that the insertion forms a loop located in the vicinity of the active site pocket and affects enzyme kinetic parameters as well as protein thermal stability. (en)
Title
  • Kinetic and structural characterization of an alternatively spliced variant of human mitochondrial 5'(3')-deoxyribonucleotidase
  • Kinetic and structural characterization of an alternatively spliced variant of human mitochondrial 5'(3')-deoxyribonucleotidase (en)
skos:prefLabel
  • Kinetic and structural characterization of an alternatively spliced variant of human mitochondrial 5'(3')-deoxyribonucleotidase
  • Kinetic and structural characterization of an alternatively spliced variant of human mitochondrial 5'(3')-deoxyribonucleotidase (en)
skos:notation
  • RIV/68378050:_____/15:00435125!RIV15-GA0-68378050
http://linked.open...avai/riv/aktivita
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  • I, P(GA203/09/0820), P(LK11205)
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  • 1
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  • 233
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  • RIV/68378050:_____/15:00435125
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  • 5'(3')-deoxyribonucleotidase; alternative splicing; crystal structure; hydrolase; mitochondria (en)
http://linked.open.../riv/klicoveSlovo
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  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [25F06E441E67]
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  • Journal of Enzyme Inhibition and Medicinal Chemistry
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  • 30
http://linked.open...iv/tvurceVysledku
  • Brynda, Jiří
  • Fábry, Milan
  • Pachl, Petr
  • Řezáčová, Pavlína
  • Veverka, Václav
http://linked.open...ain/vavai/riv/wos
  • 000347956500010
issn
  • 1475-6366
number of pages
http://bibframe.org/vocab/doi
  • 10.3109/14756366.2013.879577
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