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| | ==Crystal structure of human S100B in complex with S45== | | ==Crystal structure of human S100B in complex with S45== |
| - | <StructureSection load='3hcm' size='340' side='right' caption='[[3hcm]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3hcm' size='340' side='right'caption='[[3hcm]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3hcm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HCM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HCM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3hcm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HCM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=S45:(3R)-3-[3-(4-CHLOROPHENYL)-1,2,4-OXADIAZOL-5-YL]PIPERIDINE'>S45</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]] 2Å</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=3hcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hcm OCA], [http://pdbe.org/3hcm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hcm RCSB], [http://www.ebi.ac.uk/pdbsum/3hcm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hcm ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=S45:(3R)-3-[3-(4-CHLOROPHENYL)-1,2,4-OXADIAZOL-5-YL]PIPERIDINE'>S45</scene></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=3hcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hcm OCA], [https://pdbe.org/3hcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hcm RCSB], [https://www.ebi.ac.uk/pdbsum/3hcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hcm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/S100B_HUMAN S100B_HUMAN]] 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 (By similarity). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization.<ref>PMID:20351179</ref> | + | [https://www.uniprot.org/uniprot/S100B_HUMAN S100B_HUMAN] 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 (By similarity). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization.<ref>PMID:20351179</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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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: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Cesari, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Mangani, S]] | + | [[Category: Cesari L]] |
| - | [[Category: Calcium]] | + | [[Category: Mangani S]] |
| - | [[Category: Calcium binding protein]]
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| - | [[Category: Cytoplasm]]
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| - | [[Category: Inhibitor]]
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| - | [[Category: Metal binding protein]]
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| - | [[Category: Metal-binding]]
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| - | [[Category: Nucleus]]
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| - | [[Category: S100b]]
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| Structural highlights
Function
S100B_HUMAN 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 (By similarity). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization.[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
S100B contributes to cell proliferation by binding the C terminus of p53 and inhibiting its tumor suppressor function. The use of multiple computational approaches to screen fragment libraries targeting the human S100B-p53 interaction site is reported. This in silico screening led to the identification of 280 novel prospective ligands. NMR spectroscopic experiments revealed specific binding at the p53 interaction site for a set of these compounds and confirmed their potential for further rational optimization. The X-ray crystal structure determined for one of the binders revealed key intermolecular interactions, thus paving the way for structure-based ligand optimization.
Fragmenting the S100B-p53 Interaction: Combined Virtual/Biophysical Screening Approaches to Identify Ligands.,Agamennone M, Cesari L, Lalli D, Turlizzi E, Del Conte R, Turano P, Mangani S, Padova A ChemMedChem. 2010 Jan 13. PMID:20077460[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gilquin B, Cannon BR, Hubstenberger A, Moulouel B, Falk E, Merle N, Assard N, Kieffer S, Rousseau D, Wilder PT, Weber DJ, Baudier J. The calcium-dependent interaction between S100B and the mitochondrial AAA ATPase ATAD3A and the role of this complex in the cytoplasmic processing of ATAD3A. Mol Cell Biol. 2010 Jun;30(11):2724-36. doi: 10.1128/MCB.01468-09. Epub 2010 Mar , 29. PMID:20351179 doi:10.1128/MCB.01468-09
- ↑ Agamennone M, Cesari L, Lalli D, Turlizzi E, Del Conte R, Turano P, Mangani S, Padova A. Fragmenting the S100B-p53 Interaction: Combined Virtual/Biophysical Screening Approaches to Identify Ligands. ChemMedChem. 2010 Jan 13. PMID:20077460 doi:10.1002/cmdc.200900393
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