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  • Jemth, Ann-SofieKarolinska Institute,Karolinska Institutet (author)

Crystal Structure and Substrate Specificity of the 8-oxo-dGTP Hydrolase NUDT1 from Arabidopsis thaliana

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-01-07
  • American Chemical Society (ACS),2019
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:su-167524
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-167524URI
  • https://doi.org/10.1021/acs.biochem.8b00950DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:140364187URI
  • https://lup.lub.lu.se/record/d9f4d2ab-923b-4a0b-8dd5-6579a81c096eURI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Arabidopsis thaliana NUDT1 (AtNUDT1) belongs to the Nudix family of proteins, which have a diverse range of substrates, including oxidized nucleotides such as 8-oxo-dGTP. The hydrolysis of oxidized dNTPs is highly important as it prevents their incorporation into DNA, thus preventing mutations and DNA damage. AtNUDT1 is the sole Nudix enzyme from A. thaliana shown to have activity against 8-oxo-dGTP. We present the structure of AtNUDT1 in complex with 8-oxo-dGTP. Structural comparison with bacterial and human homologues reveals a conserved overall fold. Analysis of the 8-oxo-dGTP binding mode shows that the residues Asn76 and Ser89 interact with the 08 atom of the substrate, a feature not observed in structures of protein homologues solved to date. Kinetic analysis of wild-type and mutant AtNUDT1 confirmed that these active site residues influence 8-oxo-dGTP hydrolysis. A recent study showed that AtNUDT1 is also able to hydrolyze terpene compounds. The diversity of reactions catalyzed by AtNUDT1 suggests that this Nudix enzyme from higher plants has evolved in a manner distinct to those from other organisms.

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  • Scaletti, EmmaStockholm University,Stockholms universitet,Institutionen för biokemi och biofysik(Swepub:lu)em4772sc (author)
  • Carter, MeganStockholm University,Stockholms universitet,Institutionen för biokemi och biofysik(Swepub:su)mbult (author)
  • Helleday, ThomasKarolinska Institute,Karolinska Institutet,University of Sheffield (author)
  • Stenmark, PålStockholm University,Lunds universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Lund University, Sweden,Strukturell biokemi,Forskargrupper vid Lunds universitet,Structural Biochemistry,Lund University Research Groups(Swepub:lu)pa4463st (author)
  • Karolinska InstituteKarolinska Institutet (creator_code:org_t)

Related titles

  • In:Biochemistry: American Chemical Society (ACS)58:7, s. 887-8990006-29601520-4995

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