5htb: Difference between revisions
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The | ==Crystal structure of haspin (GSG2) in complex with bisubstrate inhibitor ARC-3353== | ||
<StructureSection load='5htb' size='340' side='right' caption='[[5htb]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5htb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HTB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HTB FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6L5:(3R)-4-AMINO-3-{[6-({[(2S,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]CARBONYL}AMINO)HEXANOYL]AMINO}-4-OXOBUTANOIC+ACID+(NON-PREFERRED+NAME)'>6L5</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=66N:L-ALANINAMIDE'>66N</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5htb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5htb OCA], [http://pdbe.org/5htb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5htb RCSB], [http://www.ebi.ac.uk/pdbsum/5htb PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Haspin is a mitotic protein kinase that is responsible for the phosphorylation of Thr3 of histone H3, thereby creating a recognition motif for docking of the chromosomal passenger complex that is crucial for the progression of cell division. Here, two high-resolution models of haspin with previously reported inhibitors consisting of an ATP analogue and a histone H3(1-7) peptide analogue are presented. The structures of the complexes confirm the bisubstrate character of the inhibitors by revealing the signature binding modes of the moieties targeting the ATP-binding site and the protein substrate-binding site of the kinase. This is the first structural model of a bisubstrate inhibitor targeting haspin. The presented structural data represent a model for the future development of more specific haspin inhibitors. | |||
Co-crystal structures of the protein kinase haspin with bisubstrate inhibitors.,Lavogina D, Kestav K, Chaikuad A, Heroven C, Knapp S, Uri A Acta Crystallogr F Struct Biol Commun. 2016 May 1;72(Pt 5):339-45. doi:, 10.1107/S2053230X16004611. Epub 2016 Apr 22. PMID:27139824<ref>PMID:27139824</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5htb" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Non-specific serine/threonine protein kinase]] | |||
[[Category: Arrowsmith, C H]] | |||
[[Category: Bountra, C]] | |||
[[Category: Chaikuad, A]] | [[Category: Chaikuad, A]] | ||
[[Category: Delft, F von]] | |||
[[Category: Edwards, A M]] | |||
[[Category: Heroven, C]] | |||
[[Category: Kestav, K]] | |||
[[Category: Knapp, S]] | |||
[[Category: Lavogina, D]] | [[Category: Lavogina, D]] | ||
[[Category: Structural genomic]] | |||
[[Category: Structural | |||
[[Category: Uri, A]] | [[Category: Uri, A]] | ||
[[Category: | [[Category: Allosteric]] | ||
[[Category: Bisubstrate inhibitor]] | |||
[[Category: Inhibitor]] | |||
[[Category: Kinase]] | |||
[[Category: Transferase]] | |||
[[Category: Transferase-transferase inhibitor complex]] | |||
Revision as of 19:55, 15 May 2016
Crystal structure of haspin (GSG2) in complex with bisubstrate inhibitor ARC-3353Crystal structure of haspin (GSG2) in complex with bisubstrate inhibitor ARC-3353
Structural highlights
Function[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.[1] [2] [3] [4] [5] Publication Abstract from PubMedHaspin is a mitotic protein kinase that is responsible for the phosphorylation of Thr3 of histone H3, thereby creating a recognition motif for docking of the chromosomal passenger complex that is crucial for the progression of cell division. Here, two high-resolution models of haspin with previously reported inhibitors consisting of an ATP analogue and a histone H3(1-7) peptide analogue are presented. The structures of the complexes confirm the bisubstrate character of the inhibitors by revealing the signature binding modes of the moieties targeting the ATP-binding site and the protein substrate-binding site of the kinase. This is the first structural model of a bisubstrate inhibitor targeting haspin. The presented structural data represent a model for the future development of more specific haspin inhibitors. Co-crystal structures of the protein kinase haspin with bisubstrate inhibitors.,Lavogina D, Kestav K, Chaikuad A, Heroven C, Knapp S, Uri A Acta Crystallogr F Struct Biol Commun. 2016 May 1;72(Pt 5):339-45. doi:, 10.1107/S2053230X16004611. Epub 2016 Apr 22. PMID:27139824[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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