6bp0: Difference between revisions

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<StructureSection load='6bp0' size='340' side='right'caption='[[6bp0]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
<StructureSection load='6bp0' size='340' side='right'caption='[[6bp0]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6bp0]] 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=6BP0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BP0 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6bp0]] 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=6BP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BP0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E1D:(7R)-2-[(3,5-difluoro-4-hydroxyphenyl)amino]-5,7,8-trimethyl-7,8-dihydropteridin-6(5H)-one'>E1D</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<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>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E1D:(7R)-2-[(3,5-difluoro-4-hydroxyphenyl)amino]-5,7,8-trimethyl-7,8-dihydropteridin-6(5H)-one'>E1D</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bp0 OCA], [https://pdbe.org/6bp0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bp0 RCSB], [https://www.ebi.ac.uk/pdbsum/6bp0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bp0 ProSAT]</span></td></tr>
<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=6bp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bp0 OCA], [http://pdbe.org/6bp0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bp0 RCSB], [http://www.ebi.ac.uk/pdbsum/6bp0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bp0 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[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.  
[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 ==
[[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>
[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>  


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Arruda P]]
[[Category: Arruda, P]]
[[Category: Azevedo A]]
[[Category: Azevedo, A]]
[[Category: Counago RM]]
[[Category: Counago, R M]]
[[Category: Edwards AM]]
[[Category: Edwards, A M]]
[[Category: Elkins J]]
[[Category: Elkins, J]]
[[Category: Ferreira M]]
[[Category: Ferreira, M]]
[[Category: Gama F]]
[[Category: Gama, F]]
[[Category: Guimaraes C]]
[[Category: Guimaraes, C]]
[[Category: Mascarello A]]
[[Category: Mascarello, A]]
[[Category: Massirer KB]]
[[Category: Massirer, K B]]
[[Category: De Souza GP]]
[[Category: Reis, C V.dos]]
[[Category: Dos Reis CV]]
[[Category: Structural genomic]]
[[Category: Souza, G P.de]]
[[Category: Protein kinase domain]]
[[Category: Sgc]]
[[Category: Transferase]]
[[Category: Transferase-transferase inhibitor complex]]

Latest revision as of 17:47, 4 October 2023

Crystal Structure of the Human vaccinia-related kinase 1 bound to (R)-2-phenylaminopteridinone inhibitorCrystal Structure of the Human vaccinia-related kinase 1 bound to (R)-2-phenylaminopteridinone inhibitor

Structural highlights

6bp0 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

VRK1_HUMAN Pontocerebellar hypoplasia type 1. The disease is caused by mutations affecting the gene represented in this entry.

Function

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.[1] [2] [3] [4] [5] [6]

See Also

References

  1. ↑ Lopez-Borges S, Lazo PA. The human vaccinia-related kinase 1 (VRK1) phosphorylates threonine-18 within the mdm-2 binding site of the p53 tumour suppressor protein. Oncogene. 2000 Jul 27;19(32):3656-64. PMID:10951572 doi:http://dx.doi.org/10.1038/sj.onc.1203709
  2. ↑ Nichols RJ, Traktman P. Characterization of three paralogous members of the Mammalian vaccinia related kinase family. J Biol Chem. 2004 Feb 27;279(9):7934-46. Epub 2003 Nov 25. PMID:14645249 doi:http://dx.doi.org/10.1074/jbc.M310813200
  3. ↑ Sevilla A, Santos CR, Vega FM, Lazo PA. Human vaccinia-related kinase 1 (VRK1) activates the ATF2 transcriptional activity by novel phosphorylation on Thr-73 and Ser-62 and cooperates with JNK. J Biol Chem. 2004 Jun 25;279(26):27458-65. Epub 2004 Apr 21. PMID:15105425 doi:http://dx.doi.org/10.1074/jbc.M401009200
  4. ↑ Nichols RJ, Wiebe MS, Traktman P. The vaccinia-related kinases phosphorylate the N' terminus of BAF, regulating its interaction with DNA and its retention in the nucleus. Mol Biol Cell. 2006 May;17(5):2451-64. Epub 2006 Feb 22. PMID:16495336 doi:http://dx.doi.org/10.1091/mbc.E05-12-1179
  5. ↑ Sanz-Garcia M, Lopez-Sanchez I, Lazo PA. Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Mol Cell Proteomics. 2008 Nov;7(11):2199-214. doi: 10.1074/mcp.M700586-MCP200., Epub 2008 Jul 9. PMID:18617507 doi:10.1074/mcp.M700586-MCP200
  6. ↑ Lopez-Sanchez I, Sanz-Garcia M, Lazo PA. Plk3 interacts with and specifically phosphorylates VRK1 in Ser342, a downstream target in a pathway that induces Golgi fragmentation. Mol Cell Biol. 2009 Mar;29(5):1189-201. doi: 10.1128/MCB.01341-08. Epub 2008 Dec , 22. PMID:19103756 doi:10.1128/MCB.01341-08

6bp0, resolution 1.90Å

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