Conformational flexibilities in malformin A

✍ Scribed by Alok K. Mitra; R. Chandrasekaran

• Publisher: Wiley (John Wiley & Sons)
• Year: 2007
• Tongue: English
• Weight: 783 KB
• Volume: 23
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.360231125

✦ Synopsis

Abstract

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 SS 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 SS 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]