4ouc

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{{STRUCTURE_4ouc| PDB=4ouc | SCENE= }}
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==Structure of human haspin in complex with histone H3 substrate==
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===Structure of human haspin in complex with histone H3 substrate===
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<StructureSection load='4ouc' size='340' side='right' caption='[[4ouc]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4ouc]] is a 2 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=4OUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OUC FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5ID:(2R,3R,4S,5R)-2-(4-AMINO-5-IODO-7H-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-(HYDROXYMETHYL)TETRAHYDROFURAN-3,4-DIOL'>5ID</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene><br>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ouc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ouc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ouc RCSB], [http://www.ebi.ac.uk/pdbsum/4ouc PDBsum]</span></td></tr>
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<table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Recent discoveries have highlighted the importance of Haspin kinase activity for the correct positioning of the kinase Aurora B at the centromere. Haspin phosphorylates Thr(3) of the histone H3 (H3), which provides a signal for Aurora B to localize to the centromere of mitotic chromosomes. To date, histone H3 is the only confirmed Haspin substrate. We used a combination of biochemical, pharmacological, and mass spectrometric approaches to study the consequences of Haspin inhibition in mitotic cells. We quantified 3964 phosphorylation sites on chromatin-associated proteins and identified a Haspin protein-protein interaction network. We determined the Haspin consensus motif and the co-crystal structure of the kinase with the histone H3 tail. The structure revealed a unique bent substrate binding mode positioning the histone H3 residues Arg(2) and Lys(4) adjacent to the Haspin phosphorylated threonine into acidic binding pockets. This unique conformation of the kinase-substrate complex explains the reported modulation of Haspin activity by methylation of Lys(4) of the histone H3. In addition, the identification of the structural basis of substrate recognition and the amino acid sequence preferences of Haspin aided the identification of novel candidate Haspin substrates. In particular, we validated the phosphorylation of Ser(137) of the histone variant macroH2A as a target of Haspin kinase activity. MacroH2A Ser(137) resides in a basic stretch of about 40 amino acids that is required to stabilize extranucleosomal DNA, suggesting that phosphorylation of Ser(137) might regulate the interactions of macroH2A and DNA. Overall, our data suggest that Haspin activity affects the phosphorylation state of proteins involved in gene expression regulation and splicing.
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==Function==
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Modulation of the chromatin phosphoproteome by the haspin protein kinase.,Maiolica A, de Medina-Redondo M, Schoof EM, Chaikuad A, Villa F, Gatti M, Jeganathan S, Lou HJ, Novy K, Hauri S, Toprak UH, Herzog F, Meraldi P, Penengo L, Turk BE, Knapp S, Linding R, Aebersold R Mol Cell Proteomics. 2014 Jul;13(7):1724-40. doi: 10.1074/mcp.M113.034819. Epub, 2014 Apr 14. PMID:24732914<ref>PMID:24732914</ref>
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[[http://www.uniprot.org/uniprot/HASP_HUMAN HASP_HUMAN]] Serine/threonine-protein kinase that phosphorylates histone H3 at 'Ser-3' (H3T3ph) during mitosis. This positions and activates AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle.<ref>PMID:11228240</ref> <ref>PMID:15681610</ref> <ref>PMID:17084365</ref> <ref>PMID:20705812</ref> <ref>PMID:20929775</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4ouc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OUC OCA].
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</div>
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==Reference==
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==See Also==
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<references group="xtra"/><references/>
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*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Human]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Arrowsmith, C H.]]
[[Category: Arrowsmith, C H.]]

Revision as of 06:19, 13 August 2014

Structure of human haspin in complex with histone H3 substrate

4ouc, resolution 1.90Å

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