3gk2

X-ray structure of bovine SBi279,Ca(2+)-S100B

spinqualitylabelsall models 3gk2, resolution 1.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3gk2 is a 1 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 27A, CA, CAC Related: 1mho, 3cr2, 3cr4, 3cr5, 1dt7, 3gk1, 3gk4 Gene: S100B (Bos taurus) Resources: FirstGlance, OCA, RCSB, PDBsum 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also S100 protein

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