1jlo

From Proteopedia

Revision as of 16:14, 20 November 2007

Solution Structure of the Noncompetitive Skeletal Muscle Nicotinic Acetylcholine Receptor Antagonist Psi-conotoxin PIIIE

Overview

A revised, high-resolution structure of psi-conotoxin Piiie (psi-Piiie), a, noncompetitive inhibitor of the nicotinic acetylcholine receptor (nAChR), produced through the use of NMR and molecular modeling calculations is, presented. The original structures of psi-Piiie had a relatively high, degree of disorder, particularly in the conformation of the disulfide, bridges. Our studies utilized (13)C-labeling of selected cysteine residues, allowing the resolution of all problems of resonance overlap for the, cysteine residues. The improved data were used to produce a new set of, structures by a molecular modeling process incorporating relaxation matrix, methods for the determination of interproton distance restraints and a, combination of distance geometry and simulated annealing for structure, generation. The structures produced are very well converged with the RMSD, of backbone atom positions of the main body of the peptide improving from, 0.73 to 0.13 A. Other indicators of correlation with the experimental data, and quality of covalent geometry showed significant improvement in the new, structures. The overall conformation of the peptide backbone is similar, between the two determinations with the exception of the N-terminus. This, difference leads to a significant effect on the predicted distribution of, positive charge within psi-Piiie, a property likely to influence, interpretation of future mutational studies.

About this Structure

1JLO is a Single protein structure of sequence from [1] with NH2 as ligand. Full crystallographic information is available from OCA.

Reference

An improved solution structure for psi-conotoxin PiiiE., Van Wagoner RM, Ireland CM, Biochemistry. 2003 Jun 3;42(21):6347-52. PMID:12767215

Page seeded by OCA on Tue Nov 20 18:22:04 2007