5l2x: Difference between revisions
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The entry | ==Crystal structure of human PrimPol ternary complex== | ||
<StructureSection load='5l2x' size='340' side='right' caption='[[5l2x]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5l2x]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L2X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L2X FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5IU:5-IODO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>5IU</scene>, <scene name='pdbligand=DDG:2,3-DIDEOXY-GUANOSINE-5-MONOPHOSPHATE'>DDG</scene></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=5l2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l2x OCA], [http://pdbe.org/5l2x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l2x RCSB], [http://www.ebi.ac.uk/pdbsum/5l2x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l2x ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/PRIPO_HUMAN PRIPO_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/PRIPO_HUMAN PRIPO_HUMAN]] DNA primase and DNA polymerase able to initiate de novo DNA synthesis using dNTPs. Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA. Involved in translesion synthesis via its primase activity by mediating uninterrupted fork progression after programmed or damage-induced fork arrest and by reinitiating DNA synthesis after dNTP depletion. Required for mitochondrial DNA (mtDNA) synthesis, suggesting it may be involved in DNA tolerance during the replication of mitochondrial DNA. Has non-overlapping function with POLH.<ref>PMID:24126761</ref> <ref>PMID:24207056</ref> <ref>PMID:24240614</ref> <ref>PMID:24267451</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
PrimPol is a novel human enzyme that contains both DNA primase and DNA polymerase activities. We present the first structure of human PrimPol in ternary complex with a DNA template-primer and an incoming deoxynucleoside triphosphate (dNTP). The ability of PrimPol to function as a DNA primase stems from a simple but remarkable feature-almost complete lack of contacts to the DNA primer strand. This, in turn, allows two dNTPs to bind initiation and elongation sites on the enzyme for the formation of the first dinucleotide. PrimPol shows the ability to synthesize DNA opposite ultraviolet (UV) lesions; however, unexpectedly, the active-site cleft of the enzyme is constrained, which precludes the bypass of UV-induced DNA lesions by conventional translesion synthesis. Together, the structure addresses long-standing questions about how DNA primases actually initiate synthesis and how primase and polymerase activities combine in a single enzyme to carry out DNA synthesis. | |||
Structure and mechanism of human PrimPol, a DNA polymerase with primase activity.,Rechkoblit O, Gupta YK, Malik R, Rajashankar KR, Johnson RE, Prakash L, Prakash S, Aggarwal AK Sci Adv. 2016 Oct 21;2(10):e1601317. eCollection 2016 Oct. PMID:27819052<ref>PMID:27819052</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5l2x" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aggarwal, A K]] | |||
[[Category: Gupta, Y K]] | |||
[[Category: Johnson, R E]] | |||
[[Category: Malik, R]] | [[Category: Malik, R]] | ||
[[Category: | [[Category: Prakash, L]] | ||
[[Category: Prakash, S]] | |||
[[Category: Rajashankar, K R]] | |||
[[Category: Rechkoblit, O]] | [[Category: Rechkoblit, O]] | ||
[[Category: | [[Category: Protein-dna complex]] | ||
[[Category: | [[Category: Transferase-dna complex]] | ||
Revision as of 13:56, 10 December 2016
Crystal structure of human PrimPol ternary complexCrystal structure of human PrimPol ternary complex
Structural highlights
Disease[PRIPO_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Function[PRIPO_HUMAN] DNA primase and DNA polymerase able to initiate de novo DNA synthesis using dNTPs. Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA. Involved in translesion synthesis via its primase activity by mediating uninterrupted fork progression after programmed or damage-induced fork arrest and by reinitiating DNA synthesis after dNTP depletion. Required for mitochondrial DNA (mtDNA) synthesis, suggesting it may be involved in DNA tolerance during the replication of mitochondrial DNA. Has non-overlapping function with POLH.[1] [2] [3] [4] Publication Abstract from PubMedPrimPol is a novel human enzyme that contains both DNA primase and DNA polymerase activities. We present the first structure of human PrimPol in ternary complex with a DNA template-primer and an incoming deoxynucleoside triphosphate (dNTP). The ability of PrimPol to function as a DNA primase stems from a simple but remarkable feature-almost complete lack of contacts to the DNA primer strand. This, in turn, allows two dNTPs to bind initiation and elongation sites on the enzyme for the formation of the first dinucleotide. PrimPol shows the ability to synthesize DNA opposite ultraviolet (UV) lesions; however, unexpectedly, the active-site cleft of the enzyme is constrained, which precludes the bypass of UV-induced DNA lesions by conventional translesion synthesis. Together, the structure addresses long-standing questions about how DNA primases actually initiate synthesis and how primase and polymerase activities combine in a single enzyme to carry out DNA synthesis. Structure and mechanism of human PrimPol, a DNA polymerase with primase activity.,Rechkoblit O, Gupta YK, Malik R, Rajashankar KR, Johnson RE, Prakash L, Prakash S, Aggarwal AK Sci Adv. 2016 Oct 21;2(10):e1601317. eCollection 2016 Oct. PMID:27819052[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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