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| | ==X-ray structure of bovine SBi523,Ca(2+)-S100B== | | ==X-ray structure of bovine SBi523,Ca(2+)-S100B== |
| - | <StructureSection load='3gk4' size='340' side='right' caption='[[3gk4]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='3gk4' size='340' side='right'caption='[[3gk4]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3gk4]] 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=3GK4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GK4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gk4]] 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=3GK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GK4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=53A:ETHYL+5-{[(1R)-1-(ETHOXYCARBONYL)-2-OXOPROPYL]SULFANYL}-1,2-DIHYDRO[1,2,3]TRIAZOLO[1,5-A]QUINAZOLINE-3-CARBOXYLATE'>53A</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]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mho|1mho]], [[3cr2|3cr2]], [[3cr4|3cr4]], [[3cr5|3cr5]], [[1dt7|1dt7]], [[3gk1|3gk1]], [[3gk2|3gk2]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=53A:ETHYL+5-{[(1R)-1-(ETHOXYCARBONYL)-2-OXOPROPYL]SULFANYL}-1,2-DIHYDRO[1,2,3]TRIAZOLO[1,5-A]QUINAZOLINE-3-CARBOXYLATE'>53A</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=3gk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gk4 OCA], [https://pdbe.org/3gk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gk4 RCSB], [https://www.ebi.ac.uk/pdbsum/3gk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gk4 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=3gk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gk4 OCA], [http://pdbe.org/3gk4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gk4 RCSB], [http://www.ebi.ac.uk/pdbsum/3gk4 PDBsum]</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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gk/3gk4_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gk/3gk4_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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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: Charpentier, T H]] | + | [[Category: Large Structures]] |
| - | [[Category: Toth, E A]] | + | [[Category: Charpentier TH]] |
| - | [[Category: Weber, D J]] | + | [[Category: Toth EA]] |
| - | [[Category: Alpha helical]] | + | [[Category: Weber DJ]] |
| - | [[Category: Ef hand]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Nucleus]]
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| 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
Structural studies are part of a rational drug design program underway to inhibit the S100B-p53 interaction and restore wild-type p53 function in malignant melanoma. To this end, structures of three compounds (SBi132, SBi1279, and SBi523) bound to Ca<sup>2+</sup>-S100B were determined by X-ray crystallography at 2.10 A (Rfree = 0.257), 1.98 A (Rfree = 0.281) and 1.90 A (Rfree = 0.228) resolution, respectively. Upon comparison, SBi132, SBi279, and SBi523 were found to bind in distinct locations/orientations within the hydrophobic target binding pocket of Ca<sup>2+</sup>-S100B with minimal structural changes observed for the protein upon complex formation with each compound. Specifically, SBi132 binds nearby residues in loop 2 (His-42, Phe-43, Leu-44) and helix 4 (Phe-76, Met-79, Ile-80, Ala-83, Cys-84, Phe-87 and Phe-88); whereas, SBi523 interacts with a separate site defined by residues within loop 2 (Ser-41, His-42, Phe-43, Leu-44, Glu-45 and Glu-46) and one residue on helix 4 (Phe-87). The SBi279 binding site on Ca<sup>2+</sup>-S100B overlaps the SBi132 and SBi523 sites and contacts residues in both loop 2 (Ser-41, His-42, Phe-43, Leu-44, Glu-45) and helix 4 (Ile-80, Ala-83, Cys-84, Phe-87 and Phe-88). NMR data, including saturation transfer difference (STD) and <sup>15</sup>N backbone and <sup>13</sup>C sidechain chemical shift perturbations were consistent with the X-ray crystal structures and demonstrated the relevance of all three small molecule-S100B complexes in solution. The discovery that SBi132, SBi279, and SBi523 bind to proximal sites on Ca<sup>2+</sup>-S100B could be useful for the development of a new class of molecule(s) that interacts with one or more of these binding sites simultaneously, thereby by yielding novel tight binding inhibitors specific for blocking protein-protein interactions involving S100B.
Small molecules bound to unique sites in the target protein binding cleft of calcium-bound S100B as characterized by nuclear magnetic resonance (NMR) and X-ray crystallography.,Charpentier TH, Wilder PT, Liriano MA, Varney KM, Zhong S, Coop A, Pozharski E, Mackerell AD, Toth EA, Weber DJ Biochemistry. 2009 May 26. PMID:19469484[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
- ↑ Charpentier TH, Wilder PT, Liriano MA, Varney KM, Zhong S, Coop A, Pozharski E, Mackerell AD, Toth EA, Weber DJ. Small molecules bound to unique sites in the target protein binding cleft of calcium-bound S100B as characterized by nuclear magnetic resonance (NMR) and X-ray crystallography. Biochemistry. 2009 May 26. PMID:19469484 doi:10.1021/bi9005754
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