Document Detail

Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis.
MedLine Citation:
PMID:  23035246     Owner:  NLM     Status:  MEDLINE    
Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5' to the abasic site. Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. Furthermore, the structural mechanism for AP-site cleavage is incomplete. Here we report a detailed structural and biochemical study of the AP endonuclease from Neisseria meningitidis that has allowed us to capture structural intermediates providing more complete snapshots of the catalytic mechanism. Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures.
Duo Lu; Jan Silhan; James T MacDonald; Elisabeth P Carpenter; Kirsten Jensen; Christoph M Tang; Geoff S Baldwin; Paul S Freemont
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-03
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-17     Completed Date:  2012-12-31     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16852-7     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
PDB/4B5F;  4B5G;  4B5H;  4B5I;  4B5J;  4B5M
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MeSH Terms
Crystallography, X-Ray
DNA / chemistry,  metabolism*
DNA Repair / genetics*
DNA-(Apurinic or Apyrimidinic Site) Lyase / chemistry*,  metabolism*
Models, Molecular*
Molecular Structure
Neisseria meningitidis / genetics*,  metabolism
Protein Conformation
Protein Folding
Grant Support
092809//Wellcome Trust; G0900888//Medical Research Council; //Wellcome Trust
Reg. No./Substance:
0/Furans; 3N8FZZ6PY4/tetrahydrofuran; 9007-49-2/DNA; EC protein, human; EC or Apyrimidinic Site) Lyase

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