A study of calicheamicin γ1
I complexed to seven different recognition sites is presented. The
recognition sites encompass a range of oligopyrimidine sites that present different topological features in the
minor groove. Intermolecular NOE networks for the different calicheamicin-DNA complexes show that the
drug binds in the same
mode to each recognition site. Calicheamicin binding also induces a set of characteristic
conformational changes in the DNA in each complex that maximize the complementarity of the fit between
calicheamicin and the DNA. Based on an analysis of the different complexes as well as biochemical information
on cleavage preferences, we propose that calicheamicin displays a shape-selective preference for pyrimidine
tracts through an induced-fit mechanism. We predict that any carbohydrate that maintains the overall shape of
the calicheamicin oligosaccharide will exhibit similar sequence selectivity. This hypothesis is supported by
experiments on calicheamicin oligosaccharide analogues reported in the following contribution.
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