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| | ==Solution structure of calcium loaded S100B complexed to a peptide from N-Terminal regulatory domain of NDR kinase.== | | ==Solution structure of calcium loaded S100B complexed to a peptide from N-Terminal regulatory domain of NDR kinase.== |
| - | <StructureSection load='1psb' size='340' side='right' caption='[[1psb]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1psb' size='340' side='right'caption='[[1psb]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1psb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PSB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PSB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1psb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PSB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PSB FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mho|1mho]], [[1dt7|1dt7]], [[1mwn|1mwn]], [[1qlk|1qlk]], [[1uwo|1uwo]], [[1mq1|1mq1]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S100B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=1psb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1psb OCA], [https://pdbe.org/1psb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1psb RCSB], [https://www.ebi.ac.uk/pdbsum/1psb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1psb ProSAT]</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=1psb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1psb OCA], [http://pdbe.org/1psb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1psb RCSB], [http://www.ebi.ac.uk/pdbsum/1psb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1psb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN]] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).<ref>PMID:14661952</ref> [[http://www.uniprot.org/uniprot/STK38_HUMAN STK38_HUMAN]] Negative regulator of MAP3K1/2 signaling. Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2.<ref>PMID:7761441</ref> <ref>PMID:12493777</ref> <ref>PMID:15197186</ref> <ref>PMID:17906693</ref> | + | [https://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).<ref>PMID:14661952</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1psb" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1psb" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[S100 proteins 3D structures|S100 proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| - | [[Category: Bhattacharya, S]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chazin, W J]] | + | [[Category: Large Structures]] |
| - | [[Category: Heizmann, C W]] | + | [[Category: Bhattacharya S]] |
| - | [[Category: Hemmings, B]] | + | [[Category: Chazin WJ]] |
| - | [[Category: Large, E]] | + | [[Category: Heizmann CW]] |
| - | [[Category: Helix-loop-helix]] | + | [[Category: Hemmings B]] |
| - | [[Category: Metal binding protein]] | + | [[Category: Large E]] |
| - | [[Category: Protein-peptide complex]]
| + | |
| Structural highlights
Function
S100B_BOVIN Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
NDR, a nuclear serine/threonine kinase, belongs to the subfamily of Dbf2 kinases that is critical to the morphology and proliferation of cells. The activity of NDR kinase is modulated in a Ca(2+)/S100B-dependent manner by phosphorylation of Ser281 in the catalytic domain and Thr444 in the C-terminal regulatory domain. S100B, which is a member of the S100 subfamily of EF-hand proteins, binds to a basic/hydrophobic sequence at the junction of the N-terminal regulatory and catalytic domains (NDR(62-87)). Unlike calmodulin-dependent kinases, regulation of NDR by S100B is not associated with direct autoinhibition of the active site, but rather involves a conformational change in the catalytic domain triggered by Ca(2+)/S100B binding to the junction region. To gain further insight into the mechanism of activation of the kinase, studies have been carried out on Ca(2+)/S100B in complex with the intact N-terminal regulatory domain, NDR(1-87). Multidimensional heteronuclear NMR analysis showed that the binding mode and stoichiometry of a peptide fragment of NDR (NDR(62-87)) is the same as for the intact N-terminal regulatory domain. The solution structure of Ca(2+)/S100B and NDR(62-87) has been determined. One target molecule is found to associate with each subunit of the S100B dimer. The peptide adopts three turns of helix in the bound state, and the complex is stabilized by both hydrophobic and electrostatic interactions. These structural studies, in combination with available biochemical data, have been used to develop a model for calcium-induced activation of NDR kinase by S100B.
Structure of the Ca2+/S100B/NDR kinase peptide complex: insights into S100 target specificity and activation of the kinase.,Bhattacharya S, Large E, Heizmann CW, Hemmings B, Chazin WJ Biochemistry. 2003 Dec 16;42(49):14416-26. PMID:14661952[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bhattacharya S, Large E, Heizmann CW, Hemmings B, Chazin WJ. Structure of the Ca2+/S100B/NDR kinase peptide complex: insights into S100 target specificity and activation of the kinase. Biochemistry. 2003 Dec 16;42(49):14416-26. PMID:14661952 doi:http://dx.doi.org/10.1021/bi035089a
- ↑ Bhattacharya S, Large E, Heizmann CW, Hemmings B, Chazin WJ. Structure of the Ca2+/S100B/NDR kinase peptide complex: insights into S100 target specificity and activation of the kinase. Biochemistry. 2003 Dec 16;42(49):14416-26. PMID:14661952 doi:http://dx.doi.org/10.1021/bi035089a
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