PDBsum entry 1kv0

Toxin

PDB id: 1kv0

Contents

Protein chains

66 a.a. *

Waters ×118

* Residue conservation analysis

References listed in PDB file

Key reference

Title

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.

Authors

R.J.Guan, Y.Xiang, X.L.He, C.G.Wang, M.Wang, Y.Zhang, E.J.Sundberg, D.C.Wang.

Ref.

J Mol Biol, 2004, 341, 1189-1204. [DOI no: 10.1016/j.jmb.2004.06.067]

PubMed id

15321715

Abstract

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.

Figure 3.

Figure 5.
Figure 5. Structure of the five-residue reverse turn and C-terminal segment in M7-A (A) and M7-B (B). In M7-A the peptide bond 9-10 adopts cis form and both NH10 and CO9 groups of the peptide are out of the reverse turn to interact with the C-terminal residues. In M7-B the group NH10 contacts neither residue 8 nor C-terminal residues in flexible state and, thus, the peptide bond 9-10 takes cis/trans co-existence. For clarity the side-chains of residues 8-12 are only shown corresponding to the cis form of the peptide 9-10, with deletion of His10 not shown in the Figures.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 341, 1189-1204) copyright 2004.