3CR5: X-ray Structure Of Bovine Pnt-zn(2+),ca(2+)-s100b

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.
PDB ID: 3CR5Download
MMDB ID: 65125
PDB Deposition Date: 2008/4/4
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.85  Å
Source Organism:
Similar Structures:
Biological Unit for 3CR5: dimeric; determined by author and by software (PISA)
Molecular Components in 3CR5
Label Count Molecule
Proteins (2 molecules)
Protein S100-b(Gene symbol: S100B)
Molecule annotation
Chemicals (10 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB