6r4t: Difference between revisions
New page: '''Unreleased structure''' The entry 6r4t is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures |
No edit summary |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of the Pri1 subunit of human primase bound to vidarabine triphosphate== | |||
<StructureSection load='6r4t' size='340' side='right'caption='[[6r4t]], [[Resolution|resolution]] 2.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6r4t]] is a 2 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=6R4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R4T 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]] 2.35Å</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=HEJ:9-{5-O-[(S)-hydroxy{[(R)-hydroxy(phosphonooxy)phosphoryl]oxy}phosphoryl]-beta-D-arabinofuranosyl}-9H-purin-6-amine'>HEJ</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=6r4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r4t OCA], [https://pdbe.org/6r4t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r4t RCSB], [https://www.ebi.ac.uk/pdbsum/6r4t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r4t 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6r4t" 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]] | |||
Latest revision as of 15:15, 24 January 2024
Crystal structure of the Pri1 subunit of human primase bound to vidarabine triphosphateCrystal structure of the Pri1 subunit of human primase bound to vidarabine triphosphate
Structural highlights
FunctionPRI1_HUMAN DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication. Publication Abstract from PubMedNucleoside 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||