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2vuw
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==Structure of human haspin kinase domain== | ==Structure of human haspin kinase domain== | ||
| - | <StructureSection load='2vuw' size='340' side='right' caption='[[2vuw]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='2vuw' size='340' side='right'caption='[[2vuw]], [[Resolution|resolution]] 1.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2vuw]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2vuw]] is a 1 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=2VUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VUW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand= | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=2vuw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vuw OCA], [https://pdbe.org/2vuw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vuw RCSB], [https://www.ebi.ac.uk/pdbsum/2vuw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vuw ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://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> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vuw ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vuw ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | The protein kinase haspin/Gsg2 plays an important role in mitosis, where it specifically phosphorylates Thr-3 in histone H3 (H3T3). Its protein sequence is only weakly homologous to other protein kinases and lacks the highly conserved motifs normally required for kinase activity. Here we report structures of human haspin in complex with ATP and the inhibitor iodotubercidin. These structures reveal a constitutively active kinase conformation, stabilized by haspin-specific inserts. Haspin also has a highly atypical activation segment well adapted for specific recognition of the basic histone tail. Despite the lack of a DFG motif, ATP binding to haspin is similar to that in classical kinases; however, the ATP gamma-phosphate forms hydrogen bonds with the conserved catalytic loop residues Asp-649 and His-651, and a His651Ala haspin mutant is inactive, suggesting a direct role for the catalytic loop in ATP recognition. Enzyme kinetic data show that haspin phosphorylates substrate peptides through a rapid equilibrium random mechanism. A detailed analysis of histone modifications in the neighborhood of H3T3 reveals that increasing methylation at Lys-4 (H3K4) strongly decreases substrate recognition, suggesting a key role of H3K4 methylation in the regulation of haspin activity. | ||
| - | + | ==See Also== | |
| - | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | |
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== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bountra | + | [[Category: Bountra C]] |
| - | [[Category: Bray | + | [[Category: Bray J]] |
| - | [[Category: Burgess-Brown | + | [[Category: Burgess-Brown N]] |
| - | + | [[Category: Edwards AM]] | |
| - | [[Category: Edwards | + | [[Category: Eswaran J]] |
| - | [[Category: Eswaran | + | [[Category: Fedorov O]] |
| - | [[Category: Fedorov | + | [[Category: Filippakopoulos P]] |
| - | [[Category: Filippakopoulos | + | [[Category: Keates T]] |
| - | [[Category: Keates | + | [[Category: King O]] |
| - | [[Category: King | + | [[Category: Knapp S]] |
| - | [[Category: Knapp | + | [[Category: Murray JW]] |
| - | [[Category: Murray | + | [[Category: Picaud S]] |
| - | [[Category: Picaud | + | [[Category: Pike ACW]] |
| - | [[Category: Pike | + | [[Category: Soundararajan M]] |
| - | [[Category: Soundararajan | + | [[Category: Wickstroem M]] |
| - | [[Category: Wickstroem | + | [[Category: Von Delft F]] |
| - | [[Category: | + | |
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Current revision
Structure of human haspin kinase domain
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Categories: Homo sapiens | Large Structures | Arrowsmith CH | Bountra C | Bray J | Burgess-Brown N | Edwards AM | Eswaran J | Fedorov O | Filippakopoulos P | Keates T | King O | Knapp S | Murray JW | Picaud S | Pike ACW | Soundararajan M | Wickstroem M | Von Delft F
