1hd7
From Proteopedia
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| - | [[Image:1hd7.jpg|left|200px]]<br /><applet load="1hd7" size=" | + | [[Image:1hd7.jpg|left|200px]]<br /><applet load="1hd7" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1hd7, resolution 1.95Å" /> | caption="1hd7, resolution 1.95Å" /> | ||
'''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 /> | '''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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==About this Structure== | ==About this Structure== | ||
| - | 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 PB 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:// | + | 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]. |
==Reference== | ==Reference== | ||
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[[Category: ref-1]] | [[Category: ref-1]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:48:36 2008'' |
Revision as of 07:48, 3 February 2008
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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
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 with as ligand. Active as DNA-(apurinic or apyrimidinic site) lyase, with EC number 4.2.99.18 Known structural/functional Site: . 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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