Gb. Trogen et al., CONFORMATIONAL STUDIES OF MICROCYSTIN-LR USING NMR-SPECTROSCOPY AND MOLECULAR-DYNAMICS CALCULATIONS, Biochemistry, 35(10), 1996, pp. 3197-3205
NMR spectroscopy in aqueous and dimethyl sulfoxide/water solutions is
used to determine the three-dimensional structures of microcystin-LR,
a cyclic cyanobacterial heptapeptide toxin which is a potent inhibitor
of type 1 and type 2A protein phosphatases. The conformations of this
toxic peptide are studied using a simulated annealing (SA) protocol f
ollowed by refined SA calculations in vacuo and free MD simulations in
water. Only one conformational family in each solvent is found. The p
eptide ring has a saddle-shaped form, essentially the same in both sol
vents. The structural difference observed between the two solution str
uctures is located to the part consisting of Mdha, Ala, and Leu. This
peptide segment is not present in nodularin, a cyclic pentapeptide of
similar toxicity. The Arg side chain is very flexible, while the side
chain of Leu is well defined. The side chain of Adda, essential for to
xicity, is constrained in the vicinity of the backbone ring but appear
s to be flexible in the more remote part.