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Conformational flexibilities in malformin A
Author(s) -
Mitra Alok K.,
Chandrasekaran R.
Publication year - 1984
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360231125
Subject(s) - chemistry , intramolecular force , pentapeptide repeat , stereochemistry , disulfide bond , hydrogen bond , cysteine , salt bridge , cyclic peptide , peptide , crystallography , molecule , enzyme , biochemistry , organic chemistry , mutant , gene
The linked‐atom‐least‐squares (LALS) technique has been applied to generate exactly cyclized and stereochemically satisfactory conformations of the cyclic pentapeptide, malformin A, which contains an intramolecular disulfide bridge across a D‐Cys—D‐Cys linkage. Consistent with theoretical, ir, and x‐ray evidence from studies on analogs of the LKiysteinyl—L‐cysteine disulfide, it is shown that the peptide bond across the SS bridge in malformin A can retain a cis configuration. The two all‐trans structures proposed earlier by A.E. Tonelli [(1978) Biopolymers 17, 1175–1179] from solution nmr data have also been analyzed. Both P‐(χ s ∼ 90°) and M‐(χ s ∼ −90°)‐type helicity of the SS bridge are found to be accessible in both the trans and the cis models in which the respective conformations of the homodetic rings are essentially preserved. The details of six different conformational states and their relative energies have been evaluated and compared. Our findings, which suggest that a variety of conformational states are accessible to malformin A, are compatible with other published results from solution studies. On the basis of hydrogen‐bonding interactions, a model is proposed to explain how malformin A might be inactivated specifically by L ‐Hyp, and not by L ‐Pro or other amino acids, as has been observed from in vivo investigations [Buckhout, T.J. & Curtis, R.W. (1976) Nature 260 , 435–436]