6dd4: Difference between revisions

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<StructureSection load='6dd4' size='340' side='right'caption='[[6dd4]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='6dd4' size='340' side='right'caption='[[6dd4]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6dd4]] 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=6DD4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DD4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6dd4]] 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=6DD4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6DD4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G6J:(7R)-2-[(3,5-difluoro-4-hydroxyphenyl)amino]-7-methyl-5,8-dipropyl-7,8-dihydropteridin-6(5H)-one'>G6J</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G6J:(7R)-2-[(3,5-difluoro-4-hydroxyphenyl)amino]-7-methyl-5,8-dipropyl-7,8-dihydropteridin-6(5H)-one'>G6J</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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='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='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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6dd4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dd4 OCA], [http://pdbe.org/6dd4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dd4 RCSB], [http://www.ebi.ac.uk/pdbsum/6dd4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dd4 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6dd4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dd4 OCA], [http://pdbe.org/6dd4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dd4 RCSB], [http://www.ebi.ac.uk/pdbsum/6dd4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dd4 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[Category: Massirer, K B]]
[[Category: Massirer, K B]]
[[Category: Reis, C V.dos]]
[[Category: Reis, C V.dos]]
[[Category: Structural genomic]]
[[Category: Santiago, A S]]
[[Category: Santiago, A S]]
[[Category: Souza, G P.de]]
[[Category: Souza, G P.de]]
[[Category: Protein kinase domain]]
[[Category: Protein kinase domain]]
[[Category: Sgc]]
[[Category: Sgc]]
[[Category: Structural genomic]]
[[Category: Transferase]]
[[Category: Transferase]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Transferase-transferase inhibitor complex]]

Revision as of 15:39, 16 December 2020

Crystal Structure of the Human vaccinia-related kinase bound to a N,N-dipropyl-dihydropteridine inhibitorCrystal Structure of the Human vaccinia-related kinase bound to a N,N-dipropyl-dihydropteridine inhibitor

Structural highlights

6dd4 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , ,
Gene:VRK1 (HUMAN)
Activity:Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
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

6dd4, resolution 2.10Å

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