5ulw: Difference between revisions
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==Structure of human DNA polymerase iota bound to template 1-methyl-deoxyadenosine== | |||
<StructureSection load='5ulw' size='340' side='right' caption='[[5ulw]], [[Resolution|resolution]] 2.62Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ulw]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ULW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ULW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=MA7:1N-METHYLADENOSINE-5-MONOPHOSPHATE'>MA7</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ulx|5ulx]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ulw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ulw OCA], [http://pdbe.org/5ulw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ulw RCSB], [http://www.ebi.ac.uk/pdbsum/5ulw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ulw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/POLI_HUMAN POLI_HUMAN]] Error-prone DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity.<ref>PMID:11013228</ref> <ref>PMID:11251121</ref> <ref>PMID:11387224</ref> <ref>PMID:12410315</ref> <ref>PMID:14630940</ref> <ref>PMID:15199127</ref> <ref>PMID:15254543</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
N1-methyl-deoxyadenosine (1-MeA) is formed by methylation of deoxyadenosine at the N1 atom. 1-MeA presents a block to replicative DNA polymerases due to its inability to participate in Watson-Crick (W-C) base pairing. Here we determine how human DNA polymerase-iota (Poliota) promotes error-free replication across 1-MeA. Steady state kinetic analyses indicate that Poliota is ~100 fold more efficient in incorporating the correct nucleotide T versus the incorrect nucleotide C opposite 1-MeA. To understand the basis of this selectivity, we determined ternary structures of Poliota bound to template 1-MeA and incoming dTTP or dCTP. In both structures, template 1-MeA rotates to the syn conformation but pairs differently with dTTP versus dCTP. Thus, whereas dTTP partakes in stable Hoogsteen base pairing with 1-MeA, dCTP fails to gain a "foothold" and is largely disordered. Together, our kinetic and structural studies show how Poliota maintains discrimination between correct and incorrect incoming nucleotide opposite 1-MeA in preserving genome integrity. | |||
Mechanism of error-free DNA synthesis across N1-methyl-deoxyadenosine by human DNA polymerase-iota.,Jain R, Choudhury JR, Buku A, Johnson RE, Prakash L, Prakash S, Aggarwal AK Sci Rep. 2017 Mar 8;7:43904. doi: 10.1038/srep43904. PMID:28272441<ref>PMID:28272441</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5ulw" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: DNA-directed DNA polymerase]] | |||
[[Category: Aggarwal, A K]] | |||
[[Category: Jain, R]] | [[Category: Jain, R]] | ||
[[Category: | [[Category: Human dna polymerase iota n1-methyl-deoxyadenosine dttp tl]] | ||
[[Category: Thansferase-dna complex]] | |||
Revision as of 16:04, 19 April 2017
Structure of human DNA polymerase iota bound to template 1-methyl-deoxyadenosineStructure of human DNA polymerase iota bound to template 1-methyl-deoxyadenosine
Structural highlights
Function[POLI_HUMAN] Error-prone DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedN1-methyl-deoxyadenosine (1-MeA) is formed by methylation of deoxyadenosine at the N1 atom. 1-MeA presents a block to replicative DNA polymerases due to its inability to participate in Watson-Crick (W-C) base pairing. Here we determine how human DNA polymerase-iota (Poliota) promotes error-free replication across 1-MeA. Steady state kinetic analyses indicate that Poliota is ~100 fold more efficient in incorporating the correct nucleotide T versus the incorrect nucleotide C opposite 1-MeA. To understand the basis of this selectivity, we determined ternary structures of Poliota bound to template 1-MeA and incoming dTTP or dCTP. In both structures, template 1-MeA rotates to the syn conformation but pairs differently with dTTP versus dCTP. Thus, whereas dTTP partakes in stable Hoogsteen base pairing with 1-MeA, dCTP fails to gain a "foothold" and is largely disordered. Together, our kinetic and structural studies show how Poliota maintains discrimination between correct and incorrect incoming nucleotide opposite 1-MeA in preserving genome integrity. Mechanism of error-free DNA synthesis across N1-methyl-deoxyadenosine by human DNA polymerase-iota.,Jain R, Choudhury JR, Buku A, Johnson RE, Prakash L, Prakash S, Aggarwal AK Sci Rep. 2017 Mar 8;7:43904. doi: 10.1038/srep43904. PMID:28272441[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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