6dd4: Difference between revisions

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'''Unreleased structure'''


The entry 6dd4 is ON HOLD
==Crystal Structure of the Human vaccinia-related kinase bound to a N,N-dipropyl-dihydropteridine inhibitor==
<StructureSection load='6dd4' size='340' side='right'caption='[[6dd4]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dd4]] 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=6DD4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DD4 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]] 2.1&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6dd4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dd4 OCA], [https://pdbe.org/6dd4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dd4 RCSB], [https://www.ebi.ac.uk/pdbsum/6dd4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dd4 ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[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>


Authors: dos Reis, C.V., Santiago, A.S., de Souza, G.P., Counago, R.M., Azevedo, A., Guimaraes, C., Mascarello, A., Gama, F., Ferreira, M., Massirer, K.B., Arruda, P., Edwards, A.M., Elkins, J.M.
==See Also==
 
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
Description: Crystal Structure of the Human vaccinia-related kinase bound to a N,N-dipropyl-dihydropteridine inhibitor
== References ==
[[Category: Unreleased Structures]]
<references/>
[[Category: Elkins, J.M]]
__TOC__
[[Category: Gama, F]]
</StructureSection>
[[Category: Massirer, K.B]]
[[Category: Homo sapiens]]
[[Category: Guimaraes, C]]
[[Category: Large Structures]]
[[Category: Counago, R.M]]
[[Category: Arruda P]]
[[Category: Santiago, A.S]]
[[Category: Azevedo A]]
[[Category: Mascarello, A]]
[[Category: Counago RM]]
[[Category: Ferreira, M]]
[[Category: Edwards AM]]
[[Category: Azevedo, A]]
[[Category: Elkins JM]]
[[Category: De Souza, G.P]]
[[Category: Ferreira M]]
[[Category: Dos Reis, C.V]]
[[Category: Gama F]]
[[Category: Edwards, A.M]]
[[Category: Guimaraes C]]
[[Category: Arruda, P]]
[[Category: Mascarello A]]
[[Category: Massirer KB]]
[[Category: Santiago AS]]
[[Category: De Souza GP]]
[[Category: Dos Reis CV]]

Latest revision as of 09:03, 11 October 2023

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 Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
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

6dd4, resolution 2.10Å

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