Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase

Jason Porta, Carol Kolar, Stanislav G. Kozmin, Youri I. Pavlov, Gloria E.O. Borgstahl

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The structure of human inosine triphosphate pyrophosphohydrolase (ITPA) has been determined using diffraction data to 1.6 Å resolution. ITPA contributes to the accurate replication of DNA by cleansing cellular dNTP pools of mutagenic nucleotide purine analogs such as dITP or dXTP. A similar high-resolution unpublished structure has been deposited in the Protein Data Bank from a monoclinic and pseudo-merohedrally twinned crystal. Here, cocrystallization of ITPA with a molar ratio of XTP appears to have improved the crystals by eliminating twinning and resulted in an orthorhombic space group. However, there was no evidence for bound XTP in the structure. Comparison with substrate-bound NTPase from a thermophilic organism predicts the movement of residues within helix α1, the loop before α6 and helix α7 to cap off the active site when substrate is bound.

Original languageEnglish (US)
Pages (from-to)1076-1081
Number of pages6
JournalActa Crystallographica Section F: Structural Biology and Crystallization Communications
Volume62
Issue number11
DOIs
StatePublished - Nov 1 2006

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Keywords

  • Inosine triphosphate pyrophosphohydrolase

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Condensed Matter Physics

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