Conformations of cysteine disulfides of peptide toxins: Advantage of differentiating forward and reverse asymmetric disulfide conformers

Abstract

Conformations of cysteine disulfides were analyzed in X-ray, nuclear magnetic resonance (NMR), and co-crystal structures of peptide toxins retrieved from Protein Data Bank. The parameters side chain torsional angles, disulfide strain energy, interatomic Cα/Cβ distances, and Ramachandran angles were used as probes to derive conformational features of cysteine disulfides. Schmidt, Ho, and Hogg (2006) Allosteric disulfide bonds. Biochemistry, 45, 7429–7433 scheme was adapted to classify the disulfide conformations of peptide toxins. Anomalies were observed while treating “forward” and “reverse” asymmetric disulfide conformers as same disulfide conformation in peptide toxins. Thus, new scheme was proposed to classify “forward” and “reverse” asymmetric disulfide conformers separately. Total available conformers space for classification of toxins disulfides is 32. Interestingly, all 32 disulfide conformations are observed in peptide toxins. –LHSpiral is predominant disulfide conformation of peptide toxins. Significant variations were observed in population of occurrence of disulfide conformers, disulfide strain energy, and distribution of D_Cα-Cα and D_Cβ-Cβ values between X-ray, NMR, and co-crystal structures of peptide toxins. The observed differences in conformations of disulfides of same peptide toxins between different states were used as platform to demonstrate advantage of differentiating forward and reverse asymmetric disulfide conformers. Newly proposed scheme allows accurate representation of true conformational diversity of disulfides between X-ray and NMR structures of same peptide toxins. Newly proposed scheme also permits to derive additional structural information from nomenclature which was illustrated by comparing conformations of disulfides between unbound and bound form of toxin with channel/receptor. The results will be of interest for growing field of structural venomics and conformational analysis of peptide/protein disulfides.

Communicated by Ramaswamy H. Sarma

Keywords:

• co-crystal structure
• disulfide conformers
• NMR structure
• peptide toxins
• X-ray structure

Acknowledgement

This article is dedicated to Prof. P. Balaram (MBU, IISc, Bangalore, India) and Late Prof. K.S. Krishnan (NCBS, Bangalore, India) for their contribution to the field of peptide toxins. We acknowledge Dr. Basavprabhu for proof-reading manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research work is funded by DST-INSPIRE faculty grant. P.Ch.V.G. and A.D. are supported by the award of a Junior Research Fellowship (JRF) from the University Grant Commission (UGC), India. AT is supported by DST-INSPIRE grant.