Kinetic barriers and ordering of non-covalently bound states.
Binding of a dimer of a glycopeptide antibiotic to two molecules of a ligand that are bound to a membrane surface (by a hydrocarbon anchor) has been investigated. This binding on a surface is cooperatively enhanced (surface enhancement) relative to the binding in solution, because the former occurs intramolecularly on a template. Previously a correlation between surface enhancement and thermodynamic stability of the dimer in free solution (Kdimsol) was hypothesised. However, we found that two weakly dimerising antibiotics (vancomycin and ristocetin A) with similar Kdimsol give very different surface enhancements. We propose a model to explain the data correlating surface enhancement to the kinetic barrier to dissociation of the dimer. The surface enhancement of binding can be expected to increase with increasing tightness of the non-covalent interactions formed at the dimer interface. The effect should be found in general where cooperativity is exercised within an organised template (e.g., DNA duplexes and proteins).
O'Brien
Simon W
SW
Cambridge Centre for Molecular Recognition, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK CB2 1EW. dhw1@cam.ac.uk
Shiozawa
Hideyuki
H
Zerella
Rosa
R
O'Brien
Dominic P
DP
Williams
Dudley H
DH
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D002240:Carbohydrate Sequence; D019281:Dimerization; D006860:Hydrogen Bonding; D007700:Kinetics; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D012996:Solutions / Q000737:chemistry; D013499:Surface Properties; D013816:Thermodynamics
D000900:Anti-Bacterial Agents; D008024:Ligands; D008051:Lipid Bilayers; D009842:Oligopeptides; D010713:Phosphatidylcholines; D012996:Solutions