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| | <StructureSection load='5er4' size='340' side='right'caption='[[5er4]], [[Resolution|resolution]] 1.81Å' scene=''> | | <StructureSection load='5er4' size='340' side='right'caption='[[5er4]], [[Resolution|resolution]] 1.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5er4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ER4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ER4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5er4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ER4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ER4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5RL:6-METHYL-5,6,6~{A},7-TETRAHYDRO-4~{H}-DIBENZO[DE,G]QUINOLINE-10,11-DIOL'>5RL</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.813Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pe7|4pe7]], [[5dkr|5dkr]], [[5er5|5er5]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5RL:6-METHYL-5,6,6~{A},7-TETRAHYDRO-4~{H}-DIBENZO[DE,G]QUINOLINE-10,11-DIOL'>5RL</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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=5er4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5er4 OCA], [https://pdbe.org/5er4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5er4 RCSB], [https://www.ebi.ac.uk/pdbsum/5er4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5er4 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=5er4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5er4 OCA], [http://pdbe.org/5er4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5er4 RCSB], [http://www.ebi.ac.uk/pdbsum/5er4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5er4 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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[S100 protein|S100 protein]] | + | *[[S100 proteins 3D structures|S100 proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Alasady, M J]] | + | [[Category: Alasady MJ]] |
| - | [[Category: Aligholizadeh, E]] | + | [[Category: Aligholizadeh E]] |
| - | [[Category: Cavalier, M C]] | + | [[Category: Cavalier MC]] |
| - | [[Category: Fang, L]] | + | [[Category: Fang L]] |
| - | [[Category: MacKerell, A D]] | + | [[Category: MacKerell Jr AD]] |
| - | [[Category: Melville, Z E]] | + | [[Category: Melville ZE]] |
| - | [[Category: Pierce, A D]] | + | [[Category: Pierce AD]] |
| - | [[Category: Weber, D J]] | + | [[Category: Weber DJ]] |
| - | [[Category: Wilder, P T]] | + | [[Category: Wilder PT]] |
| - | [[Category: Calcium binding]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Covalent inhibitor]]
| + | |
| - | [[Category: Malignant melanoma]]
| + | |
| - | [[Category: Metal binding protein-inhibitor 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]
Publication Abstract from PubMed
Structure-based drug discovery is under way to identify and develop small-molecule S100B inhibitors (SBiXs). Such inhibitors have therapeutic potential for treating malignant melanoma, since high levels of S100B downregulate wild-type p53 tumor suppressor function in this cancer. Computational and X-ray crystallographic studies of two S100B-SBiX complexes are described, and both compounds (apomorphine hydrochloride and ethidium bromide) occupy an area of the S100B hydrophobic cleft which is termed site 3. These data also reveal novel protein-inhibitor interactions which can be used in future drug-design studies to improve SBiX affinity and specificity. Of particular interest, apomorphine hydrochloride showed S100B-dependent killing in melanoma cell assays, although the efficacy exceeds its affinity for S100B and implicates possible off-target contributions. Because there are no structural data available for compounds occupying site 3 alone, these studies contribute towards the structure-based approach to targeting S100B by including interactions with residues in site 3 of S100B.
Novel protein-inhibitor interactions in site 3 of Ca(2+)-bound S100B as discovered by X-ray crystallography.,Cavalier MC, Melville Z, Aligholizadeh E, Raman EP, Yu W, Fang L, Alasady M, Pierce AD, Wilder PT, MacKerell AD Jr, Weber DJ Acta Crystallogr D Struct Biol. 2016 Jun;72(Pt 6):753-60. doi:, 10.1107/S2059798316005532. Epub 2016 May 25. PMID:27303795[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
- ↑ Cavalier MC, Melville Z, Aligholizadeh E, Raman EP, Yu W, Fang L, Alasady M, Pierce AD, Wilder PT, MacKerell AD Jr, Weber DJ. Novel protein-inhibitor interactions in site 3 of Ca(2+)-bound S100B as discovered by X-ray crystallography. Acta Crystallogr D Struct Biol. 2016 Jun;72(Pt 6):753-60. doi:, 10.1107/S2059798316005532. Epub 2016 May 25. PMID:27303795 doi:http://dx.doi.org/10.1107/S2059798316005532
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