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5kt2

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==Teranry complex of human DNA polymerase iota(26-445) inserting dCMPNPP opposite template G in the presence of Mg2+==
==Teranry complex of human DNA polymerase iota(26-445) inserting dCMPNPP opposite template G in the presence of Mg2+==
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<StructureSection load='5kt2' size='340' side='right' caption='[[5kt2]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
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<StructureSection load='5kt2' size='340' side='right'caption='[[5kt2]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5kt2]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KT2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KT2 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5kt2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KT2 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0KX:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]CYTIDINE'>0KX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.488&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kt3|5kt3]], [[5kt4|5kt4]], [[5kt5|5kt5]], [[5kt6|5kt6]], [[5kt7|5kt7]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0KX:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]CYTIDINE'>0KX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5kt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kt2 OCA], [https://pdbe.org/5kt2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kt2 RCSB], [https://www.ebi.ac.uk/pdbsum/5kt2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kt2 ProSAT]</span></td></tr>
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<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=5kt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kt2 OCA], [http://pdbe.org/5kt2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kt2 RCSB], [http://www.ebi.ac.uk/pdbsum/5kt2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kt2 ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[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>
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[https://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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DNA polymerase (pol) iota is a Y-family polymerase involved in translesion synthesis, exhibiting higher catalytic activity with Mn2+ than Mg2+. The human germline R96G variant impairs both Mn2+- and Mg2+-dependent activities of pol iota, while the Delta1-25 variant selectively enhances its Mg2+-dependent activity. We analyzed pre-steady-state kinetic and structural effects of these two metal ions and genetic variations on pol iota using pol iota core (residues 1-445) proteins. The presence of Mn2+ (0.15 mM) instead of Mg2+ (2 mM) caused a 770-fold increase in efficiency (kpol/Kd,dCTP) of pol iota for dCTP insertion opposite G, mainly due to a 450-fold decrease in Kd,dCTP. The R96G and Delta1-25 variants displayed a 53-fold decrease and a 3-fold increase, respectively, in kpol/Kd,dCTP for dCTP insertion opposite G with Mg2+ when compared to wild-type, substantially attenuated by substitution with Mn2+. Crystal structures of pol iota ternary complexes, including the primer terminus 3'-OH and a non-hydrolyzable dCTP analog opposite G with the active-site Mg2+ or Mn2+, revealed that Mn2+ achieves more optimal octahedral coordination geometry than Mg2+, with lower values in average coordination distance geometry in the catalytic metal A-site. Crystal structures of R96G revealed the loss of three H-bonds of residues Gly-96 and Tyr-93 with an incoming dNTP, due to the lack of an arginine as well as a destabilized Tyr-93 side chain secondary to the loss of a cation-pi interaction between both side chains. These results provide a mechanistic basis for alteration in pol iota catalytic function with coordinating metals and genetic variation.
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Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase iota.,Choi JY, Patra A, Yeom M, Lee YS, Zhang Q, Egli M, Guengerich FP J Biol Chem. 2016 Aug 23. pii: jbc.M116.748285. PMID:27555320<ref>PMID:27555320</ref>
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==See Also==
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*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5kt2" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: DNA-directed DNA polymerase]]
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[[Category: Homo sapiens]]
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[[Category: Choi, J Y]]
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[[Category: Large Structures]]
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[[Category: Egli, M]]
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[[Category: Synthetic construct]]
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[[Category: Guengerich, F P]]
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[[Category: Choi JY]]
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[[Category: Lee, Y S]]
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[[Category: Egli M]]
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[[Category: Patra, A]]
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[[Category: Guengerich FP]]
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[[Category: Yeom, M]]
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[[Category: Lee YS]]
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[[Category: Zhang, Q]]
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[[Category: Patra A]]
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[[Category: Dna polymerase]]
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[[Category: Yeom M]]
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[[Category: Magnesium]]
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[[Category: Zhang Q]]
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[[Category: Poli]]
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[[Category: Transferase]]
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Current revision

Teranry complex of human DNA polymerase iota(26-445) inserting dCMPNPP opposite template G in the presence of Mg2+

PDB ID 5kt2

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