5kt3

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:42, 6 March 2024) (edit) (undo)
 
(One intermediate revision not shown.)
Line 3: Line 3:
<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 ==
== Structural highlights ==
-
<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>
+
<table><tr><td colspan='2'>[[5kt3]] 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=5KT3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.64&#8491;</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='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=MN:MANGANESE+(II)+ION'>MN</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5kt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kt3 OCA], [https://pdbe.org/5kt3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kt3 RCSB], [https://www.ebi.ac.uk/pdbsum/5kt3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kt3 ProSAT]</span></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>
</table>
== Function ==
== 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>
+
[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>
-
<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.
+
-
 
+
-
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>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 5kt3" style="background-color:#fffaf0;"></div>
+
==See Also==
==See Also==
Line 28: Line 17:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: DNA-directed DNA polymerase]]
+
[[Category: Homo sapiens]]
-
[[Category: Human]]
+
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Choi, J Y]]
+
[[Category: Synthetic construct]]
-
[[Category: Egli, M]]
+
[[Category: Choi JY]]
-
[[Category: Guengerich, F P]]
+
[[Category: Egli M]]
-
[[Category: Lee, Y S]]
+
[[Category: Guengerich FP]]
-
[[Category: Patra, A]]
+
[[Category: Lee YS]]
-
[[Category: Yeom, M]]
+
[[Category: Patra A]]
-
[[Category: Zhang, Q]]
+
[[Category: Yeom M]]
-
[[Category: Dna polymerase]]
+
[[Category: Zhang Q]]
-
[[Category: Manganese]]
+
-
[[Category: Poli]]
+
-
[[Category: Transferase]]
+

Current revision

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

PDB ID 5kt3

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

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