4fqo

Crystal Structure of Calcium-Loaded S100B Bound to SBi4211

spinqualitylabelsall models 4fqo, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4fqo 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: AZ3, CA Related: 3cr4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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). Publication Abstract from PubMed Molecular Dynamics simulations of the pentamidine-S100B complex, where two molecules of pentamidine bind per monomer of S100B, were performed in an effort to determine what properties would be desirable in a pentamidine-derived compound as an inhibitor for S100B. These simulations predicted that increasing the linker length of the compound would allow a single molecule to span both pentamidine binding sites on the protein. The resulting compound, SBi4211 (also known as heptamidine), was synthesized and experiments to study its inhibition of S100B were performed. The 1.65 A X-ray crystal structure was determined for Ca(2+)-S100B-heptamdine and gives high-resolution information about key contacts that facilitate the interaction between heptamidine and S100B. Additionally, NMR HSQC experiments with both compounds show that heptamidine interacts with the same region of S100B as pentamidine. Heptamidine is able to selectively kill melanoma cells with S100B over those without S100B, indicating that its binding to S100B has an inhibitory effect and that this compound may be useful in designing higher-affinity S100B inhibitors as a treatment for melanoma and other S100B-related cancers. Structure-Based Discovery of a Novel Pentamidine-Related Inhibitor of the Calcium-Binding Protein S100B.,McKnight LE, Raman EP, Bezawada P, Kudrimoti S, Wilder PT, Hartman KG, Godoy-Ruiz R, Toth EA, Coop A, Mackerell AD Jr, Weber DJ ACS Med Chem Lett. 2012 Dec 13;3(12):975-979. Epub 2012 Sep 25. PMID:23264854 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also S100 proteins 3D structures

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