Cooperativity between ligand binding and dimerisation in a derivative of ristocetin A

Abstract

The dimerisation constant of the vancomycin group antibiotic ristocetin A has previously been shown to be lower when it is fully bound by ligand (analogues of bacterial cell wall precursors terminating in –Lys-D-Ala-D-Ala) than in its absence, i.e. dimerisation is anticooperative with ligand binding. A derivative of ristocetin A, desrhamno-ristocetin, has now been produced by enzymatic degradation, and the dimerisation constant of this derivative has been measured in the absence and presence of the bacterial cell wall precursor analogue N-acetyl-D-Ala-D-Ala. The dimerisation constant is shown to be greater in the presence of the ligand than in its absence, i.e. dimerisation is cooperative with ligand binding. This change in behaviour from anticooperativity to cooperativity is postulated to be associated with the partial equalisation of the binding affinities of the two sides of the dimer for ligand. It is therefore energetically more favourable for two ligand molecules to bind to the two halves of a desrhamno-ristocetin dimer than to two monomers.

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