Towards a three-alpha-helix bundle protein that binds volatile general anesthetics.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1130530
- author
- Manderson, Gavin LU and Johansson, Jonas S.
- publishing date
- 2004
- 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 Inc.
- external identifiers
-
- scopus:7544247028
- ISSN
- 0006-3525
- DOI
- 10.1002/bip.20138
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Connective Tissue Biology (013230151)
- id
- 17d803b4-b9aa-46d3-a3ce-79e5a20320d9 (old id 1130530)
- date added to LUP
- 2016-04-01 12:02:57
- date last changed
- 2022-01-26 22:01:53
@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}},
keywords = {{three--helix bundles; structure stability; anesthetic binding}},
language = {{eng}},
number = {{4}},
pages = {{338--354}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Biopolymers}},
title = {{Towards a three-alpha-helix bundle protein that binds volatile general anesthetics.}},
url = {{http://dx.doi.org/10.1002/bip.20138}},
doi = {{10.1002/bip.20138}},
volume = {{75}},
year = {{2004}},
}