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| | <StructureSection load='5dkn' size='340' side='right'caption='[[5dkn]], [[Resolution|resolution]] 1.53Å' scene=''> | | <StructureSection load='5dkn' size='340' side='right'caption='[[5dkn]], [[Resolution|resolution]] 1.53Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dkn]] 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=5DKN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DKN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dkn]] 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=5DKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DKN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B7I:2,2-[HEPTANE-1,7-DIYLBIS(OXYBENZENE-4,1-DIYL)]BIS(1H-IMIDAZOLE)'>B7I</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]] 1.528Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dkq|5dkq]], [[5dkr|5dkr]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B7I:2,2-[HEPTANE-1,7-DIYLBIS(OXYBENZENE-4,1-DIYL)]BIS(1H-IMIDAZOLE)'>B7I</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=5dkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dkn OCA], [https://pdbe.org/5dkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dkn RCSB], [https://www.ebi.ac.uk/pdbsum/5dkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dkn 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=5dkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dkn OCA], [http://pdbe.org/5dkn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dkn RCSB], [http://www.ebi.ac.uk/pdbsum/5dkn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dkn 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: Ansari, M I]] | + | [[Category: Ansari MI]] |
| - | [[Category: Bezawada, P]] | + | [[Category: Bezawada P]] |
| - | [[Category: Cavalier, M C]] | + | [[Category: Cavalier MC]] |
| - | [[Category: Coop, A]] | + | [[Category: Coop A]] |
| - | [[Category: MacKerell, A D]] | + | [[Category: MacKerell Jr AD]] |
| - | [[Category: McKnight, L E]] | + | [[Category: McKnight LE]] |
| - | [[Category: Neau, D B]] | + | [[Category: Neau DB]] |
| - | [[Category: Pierce, A D]] | + | [[Category: Pierce AD]] |
| - | [[Category: Raman, E P]] | + | [[Category: Raman EP]] |
| - | [[Category: Toth, E A]] | + | [[Category: Toth EA]] |
| - | [[Category: Varney, K M]] | + | [[Category: Varney KM]] |
| - | [[Category: Weber, D J]] | + | [[Category: Weber DJ]] |
| - | [[Category: Wilder, P T]] | + | [[Category: Wilder PT]] |
| - | [[Category: Calcium binding]]
| + | |
| - | [[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
The drug pentamidine inhibits calcium-dependent complex formation with p53 (CaS100B.p53) in malignant melanoma (MM) and restores p53 tumor suppressor activity in vivo. However, off-target effects associated with this drug were problematic in MM patients. Structure-activity relationship (SAR) studies were therefore completed here with 23 pentamidine analogues, and X-ray structures of CaS100B.inhibitor complexes revealed that the C-terminus of S100B adopts two different conformations, with location of Phe87 and Phe88 being the distinguishing feature and termed the "FF-gate". For symmetric pentamidine analogues (CaS100B.5a, CaS100B.6b) a channel between sites 1 and 2 on S100B was occluded by residue Phe88, but for an asymmetric pentamidine analogue (CaS100B.17), this same channel was open. The CaS100B.17 structure illustrates, for the first time, a pentamidine analog capable of binding the "open" form of the "FF-gate" and provides a means to block all three "hot spots" on CaS100B, which will impact next generation CaS100B.p53 inhibitor design.
Small Molecule Inhibitors of Ca-S100B Reveal Two Protein Conformations.,Cavalier MC, Ansari MI, Pierce AD, Wilder PT, McKnight LE, Raman EP, Neau DB, Bezawada P, Alasady MJ, Charpentier TH, Varney KM, Toth EA, MacKerell AD Jr, Coop A, Weber DJ J Med Chem. 2016 Jan 13. PMID:26727270[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, Ansari MI, Pierce AD, Wilder PT, McKnight LE, Raman EP, Neau DB, Bezawada P, Alasady MJ, Charpentier TH, Varney KM, Toth EA, MacKerell AD Jr, Coop A, Weber DJ. Small Molecule Inhibitors of Ca-S100B Reveal Two Protein Conformations. J Med Chem. 2016 Jan 13. PMID:26727270 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b01369
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