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1hd7

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[[Image:1hd7.jpg|left|200px]]<br /><applet load="1hd7" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1hd7.jpg|left|200px]]
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caption="1hd7, resolution 1.95&Aring;" />
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'''A SECOND DIVALENT METAL ION IN THE ACTIVE SITE OF A NEW CRYSTAL FORM OF HUMAN APURINIC/APYRIDINIMIC ENDONUCLEASE, APE1, AND ITS IMPLICATIONS FOR THE CATALYTIC MECHANISM'''<br />
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{{Structure
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|PDB= 1hd7 |SIZE=350|CAPTION= <scene name='initialview01'>1hd7</scene>, resolution 1.95&Aring;
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|SITE= <scene name='pdbsite=PB1:Pb+Binding+Site'>PB1</scene>
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|LIGAND= <scene name='pdbligand=PB:LEAD (II) ION'>PB</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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'''A SECOND DIVALENT METAL ION IN THE ACTIVE SITE OF A NEW CRYSTAL FORM OF HUMAN APURINIC/APYRIDINIMIC ENDONUCLEASE, APE1, AND ITS IMPLICATIONS FOR THE CATALYTIC MECHANISM'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1HD7 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=PB:'>PB</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] Known structural/functional Site: <scene name='pdbsite=PB1:Pb+Binding+Site'>PB1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HD7 OCA].
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1HD7 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=1HD7 OCA].
==Reference==
==Reference==
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Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism., Beernink PT, Segelke BW, Hadi MZ, Erzberger JP, Wilson DM 3rd, Rupp B, J Mol Biol. 2001 Apr 6;307(4):1023-34. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11286553 11286553]
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Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism., Beernink PT, Segelke BW, Hadi MZ, Erzberger JP, Wilson DM 3rd, Rupp B, J Mol Biol. 2001 Apr 6;307(4):1023-34. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11286553 11286553]
[[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: ref-1]]
[[Category: ref-1]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:00:05 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:35:35 2008''

Revision as of 09:35, 20 March 2008


PDB ID 1hd7

Drag the structure with the mouse to rotate
, resolution 1.95Å
Sites:
Ligands:
Activity: DNA-(apurinic or apyrimidinic site) lyase, with EC number 4.2.99.18
Coordinates: save as pdb, mmCIF, xml



A SECOND DIVALENT METAL ION IN THE ACTIVE SITE OF A NEW CRYSTAL FORM OF HUMAN APURINIC/APYRIDINIMIC ENDONUCLEASE, APE1, AND ITS IMPLICATIONS FOR THE CATALYTIC MECHANISM


Contents

Overview

The major human abasic endonuclease, Ape1, is an essential DNA repair enzyme that initiates the removal of apurinic/apyrimidinic sites from DNA, excises 3' replication-blocking moieties, and modulates the DNA binding activity of several transcriptional regulators. We have determined the X-ray structure of the full-length human Ape1 enzyme in two new crystal forms, one at neutral and one at acidic pH. The new structures are generally similar to the previously determined structure of a truncated Ape1 protein, but differ in the conformation of several loop regions and in spans of residues with weak electron density. While only one active-site metal ion is present in the structure determined at low pH, the structure determined from a crystal grown at the pH optimum of Ape1 nuclease activity, pH 7.5, has two metal ions bound 5 A apart in the active site. Enzyme kinetic data indicate that at least two metal-binding sites are functionally important, since Ca(2+) exhibits complex stimulatory and inhibitory effects on the Mg(2+)-dependent catalysis of Ape1, even though Ca(2+) itself does not serve as a cofactor. In conjunction, the structural and kinetic data suggest that Ape1 catalyzes hydrolysis of the DNA backbone through a two metal ion-mediated mechanism.

Disease

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

About this Structure

1HD7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism., Beernink PT, Segelke BW, Hadi MZ, Erzberger JP, Wilson DM 3rd, Rupp B, J Mol Biol. 2001 Apr 6;307(4):1023-34. PMID:11286553

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