1kv0

From Proteopedia

Revision as of 08:37, 23 January 2008

Cis/trans Isomerization of Non-prolyl Peptide Bond Observed in Crystal Structure of an Scorpion Toxin

Overview

Non-proline cis peptide bonds have been observed in numerous protein, crystal structures even though the energetic barrier to this conformation, is significant and no non-prolyl-cis/trans-isomerase has been identified, to date. While some external factors, such as metal binding or co-factor, interaction, have been identified that appear to induce cis/trans, isomerization of non-proline peptide bonds, the intrinsic structural basis, for their existence and the mechanism governing cis/trans isomerization in, proteins remains poorly understood. Here, we report the crystal structure, of a newly isolated neurotoxin, the scorpion alpha-like toxin Buthus, martensii Karsch (BmK) M7, at 1.4A resolution. BmK M7 crystallizes as a, dimer in which the identical non-proline peptide bond between residues 9, and 10 exists either in the cis conformation or as a mixture of cis and, trans conformations in either monomer. We also determined the crystal, structures of several mutants of BmK M1, a representative scorpion, alpha-like toxin that contains an identical non-proline cis peptide bond, as that observed in BmK M7, in which residues within or neighboring the, cis peptide bond were altered. Substitution of an aspartic acid residue, for lysine at residue 8 in the BmK M1 (K8D) mutant converted the cis form, of the non-proline peptide bond 9-10 into the trans form, revealing an, intramolecular switch for cis-to-trans isomerization. Cis/trans, interconversion of the switch residue at position 8 appears to be, sequence-dependent as the peptide bond between residues 9 and 10 retains, its wild-type cis conformation in the BmK M1 (K8Q) mutant structure. The, structural interconversion of the isomeric states of the BmK M1, non-proline cis peptide bond may relate to the conversion of the scorpion, alpha-toxins subgroups.

About this Structure

1KV0 is a Single protein structure of sequence from Mesobuthus martensii. Full crystallographic information is available from OCA.

Reference

Structural mechanism governing cis and trans isomeric states and an intramolecular switch for cis/trans isomerization of a non-proline peptide bond observed in crystal structures of scorpion toxins., Guan RJ, Xiang Y, He XL, Wang CG, Wang M, Zhang Y, Sundberg EJ, Wang DC, J Mol Biol. 2004 Aug 27;341(5):1189-204. PMID:15321715

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