3IQQ

X-ray structure of bovine TRTK12-Ca(2+)-S100B

3IQQ の概要

• エントリーDOI: 10.2210/pdb3iqq/pdb
• 分子名称: Protein S100-B, TRTK12 peptide, CapZ protein, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: ef hand, alpha helical, metal-binding, nucleus, metal binding protein
• 由来する生物種: Bos taurus (bovine); 詳細
• 細胞内の位置: Cytoplasm: P02638
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12239.86

構造登録者

Charpentier, T.H.,Weber, D.J.,Toth, E.A. (登録日: 2009-08-20, 公開日: 2010-02-02, 最終更新日: 2023-09-06)

主引用文献

Charpentier, T.H.,Thompson, L.E.,Liriano, M.A.,Varney, K.M.,Wilder, P.T.,Pozharski, E.,Toth, E.A.,Weber, D.J.
The Effects of CapZ Peptide (TRTK-12) Binding to S100B-Ca(2+) as Examined by NMR and X-ray Crystallography
J.Mol.Biol., 396:1227-1243, 2010

PubMed Abstract: Structure-based drug design is underway to inhibit the S100B-p53 interaction as a strategy for treating malignant melanoma. X-ray crystallography was used here to characterize an interaction between Ca(2)(+)-S100B and TRTK-12, a target that binds to the p53-binding site on S100B. The structures of Ca(2+)-S100B (1.5-A resolution) and S100B-Ca(2)(+)-TRTK-12 (2.0-A resolution) determined here indicate that the S100B-Ca(2+)-TRTK-12 complex is dominated by an interaction between Trp7 of TRTK-12 and a hydrophobic binding pocket exposed on Ca(2+)-S100B involving residues in helices 2 and 3 and loop 2. As with an S100B-Ca(2)(+)-p53 peptide complex, TRTK-12 binding to Ca(2+)-S100B was found to increase the protein's Ca(2)(+)-binding affinity. One explanation for this effect was that peptide binding introduced a structural change that increased the number of Ca(2+) ligands and/or improved the Ca(2+) coordination geometry of S100B. This possibility was ruled out when the structures of S100B-Ca(2+)-TRTK-12 and S100B-Ca(2+) were compared and calcium ion coordination by the protein was found to be nearly identical in both EF-hand calcium-binding domains (RMSD=0.19). On the other hand, B-factors for residues in EF2 of Ca(2+)-S100B were found to be significantly lowered with TRTK-12 bound. This result is consistent with NMR (15)N relaxation studies that showed that TRTK-12 binding eliminated dynamic properties observed in Ca(2+)-S100B. Such a loss of protein motion may also provide an explanation for how calcium-ion-binding affinity is increased upon binding a target. Lastly, it follows that any small-molecule inhibitor bound to Ca(2+)-S100B would also have to cause an increase in calcium-ion-binding affinity to be effective therapeutically inside a cell, so these data need to be considered in future drug design studies involving S100B.

PubMed: 20053360
DOI: 10.1016/j.jmb.2009.12.057

実験手法

X-RAY DIFFRACTION (2.01 Å)