6ac9

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==Crystal structure of human Vaccinia-related kinase 1 (VRK1) in complex with AMP-PNP==
==Crystal structure of human Vaccinia-related kinase 1 (VRK1) in complex with AMP-PNP==
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<StructureSection load='6ac9' size='340' side='right' caption='[[6ac9]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
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<StructureSection load='6ac9' size='340' side='right'caption='[[6ac9]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6ac9]] is a 4 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=6AC9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AC9 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6ac9]] is a 4 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=6AC9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AC9 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.07&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VRK1 ([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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ac9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ac9 OCA], [https://pdbe.org/6ac9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ac9 RCSB], [https://www.ebi.ac.uk/pdbsum/6ac9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ac9 ProSAT]</span></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=6ac9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ac9 OCA], [http://pdbe.org/6ac9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ac9 RCSB], [http://www.ebi.ac.uk/pdbsum/6ac9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ac9 ProSAT]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/VRK1_HUMAN VRK1_HUMAN]] Pontocerebellar hypoplasia type 1. The disease is caused by mutations affecting the gene represented in this entry.
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[https://www.uniprot.org/uniprot/VRK1_HUMAN VRK1_HUMAN] Pontocerebellar hypoplasia type 1. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/VRK1_HUMAN VRK1_HUMAN]] Serine/threonine kinase involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation. Acts by mediating phosphorylation of downstream target protein. Phosphorylates 'Thr-18' of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2. Phosphorylates casein and histone H3. Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm. Phosphorylates ATF2 which activates its transcriptional activity.<ref>PMID:10951572</ref> <ref>PMID:14645249</ref> <ref>PMID:15105425</ref> <ref>PMID:16495336</ref> <ref>PMID:18617507</ref> <ref>PMID:19103756</ref>
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[https://www.uniprot.org/uniprot/VRK1_HUMAN VRK1_HUMAN] Serine/threonine kinase involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation. Acts by mediating phosphorylation of downstream target protein. Phosphorylates 'Thr-18' of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2. Phosphorylates casein and histone H3. Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm. Phosphorylates ATF2 which activates its transcriptional activity.<ref>PMID:10951572</ref> <ref>PMID:14645249</ref> <ref>PMID:15105425</ref> <ref>PMID:16495336</ref> <ref>PMID:18617507</ref> <ref>PMID:19103756</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Vaccinia-related kinase 1 (VRK1), a serine/threonine mitotic kinase, is widely over-expressed in dividing cells and regarded as a cancer drug target primarily due to its function as an early response gene in cell proliferation. However, the mechanism of VRK1 phosphorylation and substrate activation is not well understood. More importantly even the molecular basis of VRK1 interaction with its cofactor, adenosine triphosphate (ATP), is unavailable to-date. As designing specific inhibitors remains to be the major challenge in kinase research, such a molecular understanding will enable us to design ATP-competitive specific inhibitors of VRK1. Here we report the molecular characterization of VRK1 in complex with AMP-PNP, a non-hydrolyzable ATP-analog, using NMR titration followed by the co-crystal structure determined upto 2.07 A resolution. We also carried out the structural comparison of the AMP-PNP bound-form with its apo and inhibitor-bound counterparts, which has enabled us to present our rationale toward designing VRK1-specific inhibitors.
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Crystal structure of human vaccinia-related kinase 1 in complex with AMP-PNP, a non-hydrolyzable ATP analog.,Ngow YS, Rajan S, Ye H, Yoon HS Protein Sci. 2018 Nov 21. doi: 10.1002/pro.3552. PMID:30461091<ref>PMID:30461091</ref>
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==See Also==
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6ac9" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Ngow, Y S]]
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[[Category: Ngow YS]]
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[[Category: Sreekanth, R]]
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[[Category: Sreekanth R]]
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[[Category: Yoon, H S]]
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[[Category: Yoon HS]]
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[[Category: Adenosine triphosphate]]
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[[Category: Amp-pnp]]
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[[Category: Atp]]
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[[Category: Kinase]]
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[[Category: Transferase]]
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[[Category: Vaccinia-related kinase]]
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[[Category: Vrk1]]
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Current revision

Crystal structure of human Vaccinia-related kinase 1 (VRK1) in complex with AMP-PNP

PDB ID 6ac9

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