View source for 6dtz


==Crystal structure of eukaryotic DNA primase large subunit iron-sulfur cluster domain, Y397F mutant==
<StructureSection load='6dtz' size='340' side='right'caption='[[6dtz]], [[Resolution|resolution]] 1.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dtz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DTZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DTZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.36&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene></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=6dtz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dtz OCA], [https://pdbe.org/6dtz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dtz RCSB], [https://www.ebi.ac.uk/pdbsum/6dtz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dtz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PRI2_YEAST PRI2_YEAST] DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication. In a complex with DNA polymerase alpha (DNA polymerase alpha:primase) constitutes a replicative polymerase. Both primase components participate in formation of the active center, but the ATP-binding site is exclusively located on p48.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Eukaryotic DNA primases contain a [4Fe4S] cluster in the C-terminal domain of the p58 subunit (p58C) that affects substrate affinity but is not required for catalysis. We show that, in yeast primase, the cluster serves as a DNA-mediated redox switch governing DNA binding, just as in human primase. Despite a different structural arrangement of tyrosines to facilitate electron transfer between the DNA substrate and [4Fe4S] cluster, in yeast, mutation of tyrosines Y395 and Y397 alters the same electron transfer chemistry and redox switch. Mutation of conserved tyrosine 395 diminishes the extent of p58C participation in normal redox-switching reactions, whereas mutation of conserved tyrosine 397 causes oxidative cluster degradation to the [3Fe4S](+) species during p58C redox signaling. Switching between oxidized and reduced states in the presence of the Y397 mutations thus puts primase [4Fe4S] cluster integrity and function at risk. Consistent with these observations, we find that yeast tolerate mutations to Y395 in p58C, but the single-residue mutation Y397L in p58C is lethal. Our data thus show that a constellation of tyrosines for protein-DNA electron transfer mediates the redox switch in eukaryotic primases and is required for primase function in vivo.

Yeast require redox switching in DNA primase.,O'Brien E, Salay LE, Epum EA, Friedman KL, Chazin WJ, Barton JK Proc Natl Acad Sci U S A. 2018 Dec 12. pii: 1810715115. doi:, 10.1073/pnas.1810715115. PMID:30541886<ref>PMID:30541886</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6dtz" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Chazin WJ]]
[[Category: Salay LE]]