1de9

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[[Image:1de9.gif|left|200px]]<br /><applet load="1de9" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1de9.gif|left|200px]]
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caption="1de9, resolution 3.0&Aring;" />
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'''HUMAN APE1 ENDONUCLEASE WITH BOUND ABASIC DNA AND MN2+ ION'''<br />
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{{Structure
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|PDB= 1de9 |SIZE=350|CAPTION= <scene name='initialview01'>1de9</scene>, resolution 3.0&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=MN:MANGANESE (II) ION'>MN</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/DNA-(apurinic_or_apyrimidinic_site)_lyase DNA-(apurinic or apyrimidinic site) lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.99.18 4.2.99.18]
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|GENE=
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}}
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'''HUMAN APE1 ENDONUCLEASE WITH BOUND ABASIC DNA AND MN2+ ION'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1DE9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MN:'>MN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/DNA-(apurinic_or_apyrimidinic_site)_lyase DNA-(apurinic or apyrimidinic site) lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.99.18 4.2.99.18] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DE9 OCA].
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1DE9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DE9 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10667800 10667800]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/10667800 10667800]
[[Category: DNA-(apurinic or apyrimidinic site) lyase]]
[[Category: DNA-(apurinic or apyrimidinic site) lyase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: enzyme:dna complex]]
[[Category: enzyme:dna complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:15:44 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:37:08 2008''

Revision as of 08:37, 20 March 2008


PDB ID 1de9

Drag the structure with the mouse to rotate
, resolution 3.0Å
Ligands:
Activity: DNA-(apurinic or apyrimidinic site) lyase, with EC number 4.2.99.18
Coordinates: save as pdb, mmCIF, xml



HUMAN APE1 ENDONUCLEASE WITH BOUND ABASIC DNA AND MN2+ ION


Contents

Overview

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.

Disease

Known diseases associated with this structure: Autoimmune polyglandular disease, type I OMIM:[607358], Sveinsson choreoretinal atrophy OMIM:[189967]

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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