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Towards a three‐α‐helix bundle protein that binds volatile general anesthetics
Author(s) -
Manderson Gavin A.,
Johansson Jonas S.
Publication year - 2004
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20138
Subject(s) - chemistry , helix (gastropod) , helix bundle , methionine , stereochemistry , anesthetic , alanine , side chain , tryptophan , ligand (biochemistry) , crystallography , protein structure , amino acid , biophysics , receptor , biochemistry , organic chemistry , biology , psychology , ecology , psychiatry , snail , polymer
The general anesthetics halothane and chloroform are capable of binding to synthetic water‐soluble four‐α‐helix bundles, which model the putative in vivo receptors. In this study, we investigate the binding of these anesthetics to synthetic water‐soluble three‐α‐helix bundles. A series of variants containing up to four X‐to‐Ala and up to four X‐to‐Met substitutions was made; and the effect of these substitutions on structure, stability and anesthetic binding affinity was examined. Generally, the amount of α‐helix and the stability of the three‐α‐helix bundles decreased as the number of X‐to‐Ala substitutions increased. A concomitant red‐shift in tryptophan fluorescence λ max was seen, suggesting an increased flexibility of the native structure. Up to four X‐to‐Met substitutions had little effect on the amount of α‐helix, but an increase in tryptophan λ max was seen for the variants with three and four methionine substitutions. The exceptions were a) a variant with a clustering of alanine and methionine residues at one end of the three‐α‐helix bundle, suggesting a gate structure that can admit ligand molecules; and b) a variant with a single Leu35Ala substitution, suggesting that at select positions, the size of the side chain is important for defining anesthetic binding affinity. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004