View source for 6rb4


==Crystal structure of the Pri1 subunit of human primase==
<StructureSection load='6rb4' size='340' side='right'caption='[[6rb4]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rb4]] 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=6RB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RB4 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]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6rb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rb4 OCA], [https://pdbe.org/6rb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rb4 RCSB], [https://www.ebi.ac.uk/pdbsum/6rb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rb4 ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
Nucleoside analogues are widely used in clinical practice as chemotherapy drugs. Arabinose nucleoside derivatives such as fludarabine are effective in the treatment of patients with acute and chronic leukemias and non-Hodgkin's lymphomas. Although nucleoside analogues are generally known to function by inhibiting DNA synthesis in rapidly proliferating cells, the identity of their in vivo targets and mechanism of action are often not known in molecular detail. Here we provide a structural basis for arabinose nucleotide-mediated inhibition of human primase, the DNA-dependent RNA polymerase responsible for initiation of DNA synthesis in DNA replication. Our data suggest ways in which the chemical structure of fludarabine could be modified to improve its specificity and affinity toward primase, possibly leading to less toxic and more effective therapeutic agents.

Structural Basis for Inhibition of Human Primase by Arabinofuranosyl Nucleoside Analogues Fludarabine and Vidarabine.,Holzer S, Rzechorzek NJ, Short IR, Jenkyn-Bedford M, Pellegrini L, Kilkenny ML ACS Chem Biol. 2019 Sep 20;14(9):1904-1912. doi: 10.1021/acschembio.9b00367. Epub , 2019 Sep 11. PMID:31479243<ref>PMID:31479243</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rb4" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kilkenny ML]]
[[Category: Pellegrini L]]