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5kt3

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Revision as of 08:55, 18 December 2019

Teranry complex of human DNA polymerase iota(26-445) inserting dCMPNPP opposite template G in the presence of Mn2+

Structural highlights

5kt3 is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	5kt2, 5kt4, 5kt5, 5kt6, 5kt7
Gene:	POLI, RAD30B (HUMAN)
Activity:	DNA-directed DNA polymerase, with EC number 2.7.7.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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.

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^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tissier A, Frank EG, McDonald JP, Iwai S, Hanaoka F, Woodgate R. Misinsertion and bypass of thymine-thymine dimers by human DNA polymerase iota. EMBO J. 2000 Oct 2;19(19):5259-66. PMID:11013228 doi:http://dx.doi.org/10.1093/emboj/19.19.5259
↑ Bebenek K, Tissier A, Frank EG, McDonald JP, Prasad R, Wilson SH, Woodgate R, Kunkel TA. 5'-Deoxyribose phosphate lyase activity of human DNA polymerase iota in vitro. Science. 2001 Mar 16;291(5511):2156-9. PMID:11251121 doi:http://dx.doi.org/10.1126/science.1058386
↑ Frank EG, Tissier A, McDonald JP, Rapic-Otrin V, Zeng X, Gearhart PJ, Woodgate R. Altered nucleotide misinsertion fidelity associated with poliota-dependent replication at the end of a DNA template. EMBO J. 2001 Jun 1;20(11):2914-22. PMID:11387224 doi:http://dx.doi.org/10.1093/emboj/20.11.2914
↑ Faili A, Aoufouchi S, Flatter E, Gueranger Q, Reynaud CA, Weill JC. Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota. Nature. 2002 Oct 31;419(6910):944-7. PMID:12410315 doi:http://dx.doi.org/10.1038/nature01117
↑ Haracska L, Prakash L, Prakash S. A mechanism for the exclusion of low-fidelity human Y-family DNA polymerases from base excision repair. Genes Dev. 2003 Nov 15;17(22):2777-85. PMID:14630940 doi:10.1101/gad.1146103
↑ Washington MT, Minko IG, Johnson RE, Wolfle WT, Harris TM, Lloyd RS, Prakash S, Prakash L. Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases iota and kappa. Mol Cell Biol. 2004 Jul;24(13):5687-93. PMID:15199127 doi:http://dx.doi.org/10.1128/MCB.24.13.5687-5693.2004
↑ Nair DT, Johnson RE, Prakash S, Prakash L, Aggarwal AK. Replication by human DNA polymerase-iota occurs by Hoogsteen base-pairing. Nature. 2004 Jul 15;430(6997):377-80. PMID:15254543 doi:10.1038/nature02692
↑ Choi JY, Patra A, Yeom M, Lee YS, Zhang Q, Egli M, Guengerich FP. Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase iota. J Biol Chem. 2016 Aug 23. pii: jbc.M116.748285. PMID:27555320 doi:http://dx.doi.org/10.1074/jbc.M116.748285

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5kt3"

@@ Line 1: / Line 1: @@
 ==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=''>
+<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>
+<table><tr><td colspan='2'>[[5kt3]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POLI, RAD30B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5kt3" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 == References ==
 <references/>
@@ Line 25: / Line 29: @@
 </StructureSection>
 [[Category: DNA-directed DNA polymerase]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Choi, J Y]]
 [[Category: Egli, M]]

5kt3

From Proteopedia

Revision as of 08:55, 18 December 2019

Teranry complex of human DNA polymerase iota(26-445) inserting dCMPNPP opposite template G in the presence of Mn2+

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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