1de9

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{{STRUCTURE_1de9| PDB=1de9 | SCENE= }}
{{STRUCTURE_1de9| PDB=1de9 | SCENE= }}
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'''HUMAN APE1 ENDONUCLEASE WITH BOUND ABASIC DNA AND MN2+ ION'''
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===HUMAN APE1 ENDONUCLEASE WITH BOUND ABASIC DNA AND MN2+ ION===
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==Overview==
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Non-coding apurinic/apyrimidinic (AP) sites in DNA are continually created in cells both spontaneously and by damage-specific DNA glycosylases. The biologically critical human base excision repair enzyme APE1 cleaves the DNA sugar-phosphate backbone at a position 5' of AP sites to prime DNA repair synthesis. Here we report three co-crystal structures of human APE1 bound to abasic DNA which show that APE1 uses a rigid, pre-formed, positively charged surface to kink the DNA helix and engulf the AP-DNA strand. APE1 inserts loops into both the DNA major and minor grooves and binds a flipped-out AP site in a pocket that excludes DNA bases and racemized beta-anomer AP sites. Both the APE1 active-site geometry and a complex with cleaved AP-DNA and Mn2+ support a testable structure-based catalytic mechanism. Alanine substitutions of the residues that penetrate the DNA helix unexpectedly show that human APE1 is structurally optimized to retain the cleaved DNA product. These structural and mutational results show how APE1 probably displaces bound glycosylases and retains the nicked DNA product, suggesting that APE1 acts in vivo to coordinate the orderly transfer of unstable DNA damage intermediates between the excision and synthesis steps of DNA repair.
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{{ABSTRACT_PUBMED_10667800}}
==About this Structure==
==About this Structure==
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[[Category: Dna repair abasic site]]
[[Category: Dna repair abasic site]]
[[Category: Enzyme:dna complex]]
[[Category: Enzyme:dna complex]]
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Revision as of 19:53, 30 June 2008

Image:1de9.png

Template:STRUCTURE 1de9

HUMAN APE1 ENDONUCLEASE WITH BOUND ABASIC DNA AND MN2+ ION

Template:ABSTRACT PUBMED 10667800

About this Structure

1DE9 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected], Mol CD, Izumi T, Mitra S, Tainer JA, Nature. 2000 Jan 27;403(6768):451-6. PMID:10667800

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