Document Detail

The inositol polyphosphate 5-phosphatases and the apurinic/apyrimidinic base excision repair endonucleases share a common mechanism for catalysis.
MedLine Citation:
PMID:  10962003     Owner:  NLM     Status:  MEDLINE    
Inositol polyphosphate 5-phosphatases (5-phosphatase) hydrolyze the 5-position phosphate from the inositol ring of phosphatidylinositol-derived signaling molecules; however, the mechanism of catalysis is only partially characterized. These enzymes play critical roles in regulating cell growth, apoptosis, intracellular calcium oscillations, and post-synaptic vesicular trafficking. The UCLA fold recognition server (threader) predicted that the conserved 300-amino acid catalytic domain, common to all 5-phosphatases, adopts the fold of the apurinic/apyrimidinic (AP) base excision repair endonucleases. PSI-BLAST searches of GENPEPT, using the amino acid sequence of AP endonuclease exonuclease III, identified all members of the 5-phosphatase family with highly significant scores. A sequence alignment between exonuclease III and all known 5-phosphatases revealed six highly conserved motifs containing residues that corresponded to the catalytic residues in the AP endonucleases. Mutation of each of these residues to alanine in the mammalian 43-kDa, or yeast Inp52p 5-phosphatase, resulted in complete loss of enzyme activity. We predict the 5-phosphatase enzymes share a similar mechanism of catalysis to the AP endonucleases, consistent with other common functional similarities such as an absolute requirement for magnesium for activity. Based on this analysis, functional roles have been assigned to conserved residues in all 5-phosphatase enzymes.
J C Whisstock; S Romero; R Gurung; H Nandurkar; L M Ooms; S P Bottomley; C A Mitchell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2001-01-08     Completed Date:  2001-01-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  37055-61     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
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MeSH Terms
Amino Acid Sequence
Carbon-Oxygen Lyases / metabolism*
Crystallography, X-Ray
DNA Repair*
DNA-(Apurinic or Apyrimidinic Site) Lyase
Deoxyribonuclease IV (Phage T4-Induced)
Gene Library
Models, Molecular
Molecular Sequence Data
Phosphoric Monoester Hydrolases / metabolism*
Protein Conformation
Sequence Alignment
Reg. No./Substance:
EC IV (Phage T4-Induced); EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC,4,5-trisphosphate 5-phosphatase; EC 4.2.-/Carbon-Oxygen Lyases; EC or Apyrimidinic Site) Lyase

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