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Towards a three-alpha-helix bundle protein that binds volatile general anesthetics.

Manderson, Gavin LU and Johansson, Jonas S. (2004) In Biopolymers 75(4). p.338-354
Abstract
The general anesthetics halothane and chloroform are capable of binding to synthetic water-soluble four--helix bundles, which model the putative in vivo receptors. In this study, we investigate the binding of these anesthetics to synthetic water-soluble three--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 -helix and the stability of the three--helix bundles decreased as the number of X-to-Ala substitutions increased. A concomitant red-shift in tryptophan fluorescence max was seen, suggesting an increased flexibility of the native structure.... (More)
The general anesthetics halothane and chloroform are capable of binding to synthetic water-soluble four--helix bundles, which model the putative in vivo receptors. In this study, we investigate the binding of these anesthetics to synthetic water-soluble three--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 -helix and the stability of the three--helix bundles decreased as the number of X-to-Ala substitutions increased. A concomitant red-shift in tryptophan fluorescence 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 -helix, but an increase in tryptophan 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--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. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
three--helix bundles, structure stability, anesthetic binding
in
Biopolymers
volume
75
issue
4
pages
338 - 354
publisher
John Wiley & Sons
external identifiers
  • scopus:7544247028
ISSN
0006-3525
DOI
10.1002/bip.20138
language
English
LU publication?
no
id
17d803b4-b9aa-46d3-a3ce-79e5a20320d9 (old id 1130530)
date added to LUP
2008-06-23 11:02:01
date last changed
2017-01-01 04:47:17
@article{17d803b4-b9aa-46d3-a3ce-79e5a20320d9,
  abstract     = {The general anesthetics halothane and chloroform are capable of binding to synthetic water-soluble four--helix bundles, which model the putative in vivo receptors. In this study, we investigate the binding of these anesthetics to synthetic water-soluble three--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 -helix and the stability of the three--helix bundles decreased as the number of X-to-Ala substitutions increased. A concomitant red-shift in tryptophan fluorescence 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 -helix, but an increase in tryptophan 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--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.},
  author       = {Manderson, Gavin and Johansson, Jonas S.},
  issn         = {0006-3525},
  keyword      = {three--helix bundles,structure stability,anesthetic binding},
  language     = {eng},
  number       = {4},
  pages        = {338--354},
  publisher    = {John Wiley & Sons},
  series       = {Biopolymers},
  title        = {Towards a three-alpha-helix bundle protein that binds volatile general anesthetics.},
  url          = {http://dx.doi.org/10.1002/bip.20138},
  volume       = {75},
  year         = {2004},
}