3CR4

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

Summary for 3CR4

• Entry DOI: 10.2210/pdb3cr4/pdb
• Related: 3CR2 3CR5
• Descriptor: Protein S100-B, 1,5-BIS(4-AMIDINOPHENOXY)PENTANE, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: ef hand, alpha helical, metal-binding, nucleus, metal binding protein
• Biological source: Bos taurus (Bovine)
• Cellular location: Cytoplasm: P02638
• Total number of polymer chains: 1
• Total formula weight: 11442.97

Authors

Charpentier, T.H. (deposition date: 2008-04-04, release date: 2008-08-05, Last modification date: 2024-02-21)

Primary citation

Charpentier, T.H.,Wilder, P.T.,Liriano, M.A.,Varney, K.M.,Pozharski, E.,MacKerell, A.D.,Coop, A.,Toth, E.A.,Weber, D.J.
Divalent metal ion complexes of S100B in the absence and presence of pentamidine.
J.Mol.Biol., 382:56-73, 2008

PubMed Abstract: As part of an effort to inhibit S100B, structures of pentamidine (Pnt) bound to Ca(2+)-loaded and Zn(2+),Ca(2+)-loaded S100B were determined by X-ray crystallography at 2.15 A (R(free)=0.266) and 1.85 A (R(free)=0.243) resolution, respectively. These data were compared to X-ray structures solved in the absence of Pnt, including Ca(2+)-loaded S100B and Zn(2+),Ca(2+)-loaded S100B determined here (1.88 A; R(free)=0.267). In the presence and absence of Zn(2+), electron density corresponding to two Pnt molecules per S100B subunit was mapped for both drug-bound structures. One Pnt binding site (site 1) was adjacent to a p53 peptide binding site on S100B (+/-Zn(2+)), and the second Pnt molecule was mapped to the dimer interface (site 2; +/-Zn(2+)) and in a pocket near residues that define the Zn(2+) binding site on S100B. In addition, a conformational change in S100B was observed upon the addition of Zn(2+) to Ca(2+)-S100B, which changed the conformation and orientation of Pnt bound to sites 1 and 2 of Pnt-Zn(2+),Ca(2+)-S100B when compared to Pnt-Ca(2+)-S100B. That Pnt can adapt to this Zn(2+)-dependent conformational change was unexpected and provides a new mode for S100B inhibition by this drug. These data will be useful for developing novel inhibitors of both Ca(2+)- and Ca(2+),Zn(2+)-bound S100B.

PubMed: 18602402
DOI: 10.1016/j.jmb.2008.06.047

Experimental method

X-RAY DIFFRACTION (2.15 Å)