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| | ==Crystal structure of the catalytic subunit of human primase== | | ==Crystal structure of the catalytic subunit of human primase== |
| - | <StructureSection load='4lik' size='340' side='right' caption='[[4lik]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4lik' size='340' side='right'caption='[[4lik]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lik]] is a 1 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=4LIK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LIK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lik]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LIK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LIK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lil|4lil]], [[4lim|4lim]]</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=4lik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lik OCA], [https://pdbe.org/4lik PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lik RCSB], [https://www.ebi.ac.uk/pdbsum/4lik PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lik ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4lik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lik OCA], [http://pdbe.org/4lik PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lik RCSB], [http://www.ebi.ac.uk/pdbsum/4lik PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lik ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PRI1_HUMAN PRI1_HUMAN]] DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication. | + | [https://www.uniprot.org/uniprot/PRI1_HUMAN PRI1_HUMAN] DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[RNA polymerase|RNA polymerase]] | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chazin, W J]] | + | [[Category: Large Structures]] |
| - | [[Category: Eichman, B F]] | + | [[Category: Chazin WJ]] |
| - | [[Category: Vaithiyalingam, S]] | + | [[Category: Eichman BF]] |
| - | [[Category: Prim fold]] | + | [[Category: Vaithiyalingam S]] |
| - | [[Category: Transferase]]
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| Structural highlights
Function
PRI1_HUMAN DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication.
Publication Abstract from PubMed
DNA replication in all organisms requires polymerases to synthesize copies of the genome. DNA polymerases are unable to function on a bare template and require a primer. Primases are crucial RNA polymerases that perform the initial de novo synthesis, generating the first 8-10 nucleotides of the primer. Although structures of archaeal and bacterial primases have provided insights into general priming mechanisms, these proteins are not well conserved with heterodimeric (p48/p58) primases in eukaryotes. Here, we present X-ray crystal structures of the catalytic engine of a eukaryotic primase, which is contained in the p48 subunit. The structures of p48 reveal that eukaryotic primases maintain the conserved catalytic prim fold domain, but with a unique subdomain not found in the archaeal and bacterial primases. Calorimetry experiments reveal that Mn2+ but not Mg2+ significantly enhances the binding of nucleotide to primase, which correlates with higher catalytic efficiency in vitro. The structure of p48 with bound UTP and Mn2+ provides insights into the mechanism of nucleotide synthesis by primase. Substitution of conserved residues involved in either metal or nucleotide binding alter nucleotide binding affinities, and yeast strains containing the corresponding Pri1p substitutions are not viable. Our results reveal that two residues (S160 and H166) in direct contact with the nucleotide were previously unrecognized as critical to the human primase active site. Comparing p48 structures to those of similar polymerases in different states of action suggests changes that would be required to attain a catalytically competent conformation capable of initiating dinucleotide synthesis.
Insights into Eukaryotic Primer Synthesis from Structures of the p48 Subunit of Human DNA Primase.,Vaithiyalingam S, Arnett DR, Aggarwal A, Eichman BF, Fanning E, Chazin WJ J Mol Biol. 2013 Nov 13. pii: S0022-2836(13)00718-3. doi:, 10.1016/j.jmb.2013.11.007. PMID:24239947[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Vaithiyalingam S, Arnett DR, Aggarwal A, Eichman BF, Fanning E, Chazin WJ. Insights into Eukaryotic Primer Synthesis from Structures of the p48 Subunit of Human DNA Primase. J Mol Biol. 2013 Nov 13. pii: S0022-2836(13)00718-3. doi:, 10.1016/j.jmb.2013.11.007. PMID:24239947 doi:http://dx.doi.org/10.1016/j.jmb.2013.11.007
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