TY - JOUR
T1 - Cooperativity and anti-cooperativity between ligand binding and the dimerization of ristocetin A
T2 - Asymmetry of a homodimer complex and implications for signal transduction
AU - Cho, Younghoon R.
AU - Maguire, Alison J.
AU - Try, Andrew C.
AU - Westwell, Martin S.
AU - Groves, Patrick
AU - Williams, Dudley H.
PY - 1996
Y1 - 1996
N2 - Background: Recent work has indicated that dimerization is important in the mode of action of the vancomycin group of glycopeptide antibiotics. NMR studies have shown that one member of this group, ristocetin A, forms an asymmetric dimer with two physically different binding sites for cell wall peptides. Ligand binding by ristocetin A and dimerization are slightly anti-cooperative. In contrast, for the other glycopeptide antibiotics of the vancomycin group that have been examined so far, binding of cell wall peptides and dimerization are cooperative. Results: Here we show that the two halves of the asymmetric homodimer formed by ristocetin A have different affinities for ligand binding. One of these sites is preferentially filled before the other, and binding to this site is cooperative with dimerization. Ligand binding to the other, less favored half of the dimer, is anti-cooperative with dimerization. Conclusions: In dimer complexes, anti-cooperativity of dimerization upon ligand binding can be a result of asymmetry, in which two binding sites have different affinities for ligands. Such a system, in which one binding site is filled preferentially, may be a mechanism by which the cooperativity between ligand binding and dimerization is fine tuned and may thus have relevance to the control of signal transduction in biological systems.
AB - Background: Recent work has indicated that dimerization is important in the mode of action of the vancomycin group of glycopeptide antibiotics. NMR studies have shown that one member of this group, ristocetin A, forms an asymmetric dimer with two physically different binding sites for cell wall peptides. Ligand binding by ristocetin A and dimerization are slightly anti-cooperative. In contrast, for the other glycopeptide antibiotics of the vancomycin group that have been examined so far, binding of cell wall peptides and dimerization are cooperative. Results: Here we show that the two halves of the asymmetric homodimer formed by ristocetin A have different affinities for ligand binding. One of these sites is preferentially filled before the other, and binding to this site is cooperative with dimerization. Ligand binding to the other, less favored half of the dimer, is anti-cooperative with dimerization. Conclusions: In dimer complexes, anti-cooperativity of dimerization upon ligand binding can be a result of asymmetry, in which two binding sites have different affinities for ligands. Such a system, in which one binding site is filled preferentially, may be a mechanism by which the cooperativity between ligand binding and dimerization is fine tuned and may thus have relevance to the control of signal transduction in biological systems.
KW - Anti-cooperativity
KW - Asymmetry
KW - Dimerization
KW - Ristocetin A
UR - http://www.scopus.com/inward/record.url?scp=0030090135&partnerID=8YFLogxK
M3 - Article
C2 - 8807847
AN - SCOPUS:0030090135
SN - 1074-5521
VL - 3
SP - 207
EP - 215
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 3
ER -