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'''Unreleased structure'''


The entry 5kt3 is ON HOLD
==Teranry complex of human DNA polymerase iota(26-445) inserting dCMPNPP opposite template G in the presence of Mn2+==
<StructureSection load='5kt3' size='340' side='right' caption='[[5kt3]], [[Resolution|resolution]] 2.64&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kt3]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KT3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KT3 FirstGlance]. <br>
</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=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kt2|5kt2]], [[5kt4|5kt4]], [[5kt5|5kt5]], [[5kt6|5kt6]], [[5kt7|5kt7]]</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=5kt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kt3 OCA], [http://pdbe.org/5kt3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kt3 RCSB], [http://www.ebi.ac.uk/pdbsum/5kt3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kt3 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 ==
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.


Authors: Choi, J.Y., Patra, A., Yeom, M., Lee, Y.S., Zhang, Q., Egli, M., Guengerich, F.P.
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>


Description: Teranry complex of human DNA polymerase iota(26-445) inserting dCMPNPP opposite template G in the presence of Mn2+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Lee, Y.S]]
<div class="pdbe-citations 5kt3" style="background-color:#fffaf0;"></div>
[[Category: Guengerich, F.P]]
== References ==
[[Category: Choi, J.Y]]
<references/>
[[Category: Yeom, M]]
__TOC__
</StructureSection>
[[Category: DNA-directed DNA polymerase]]
[[Category: Choi, J Y]]
[[Category: Egli, M]]
[[Category: Egli, M]]
[[Category: Guengerich, F P]]
[[Category: Lee, Y S]]
[[Category: Patra, A]]
[[Category: Patra, A]]
[[Category: Yeom, M]]
[[Category: Zhang, Q]]
[[Category: Zhang, Q]]
[[Category: Dna polymerase]]
[[Category: Manganese]]
[[Category: Poli]]
[[Category: Transferase]]
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