Effect of Four-alpha-Helix Bundle Cavity Size on Volatile Anesthetic Binding Energetics.
(2003) In Biochemistry 42(38). p.11203-11213- Abstract
- Currently, it is thought that inhalational anesthetics cause anesthesia by binding to ligand-gated ion channels. This is being investigated using four-alpha-helix bundles, small water-soluble analogues of the transmembrane domains of the "natural" receptor proteins. The study presented here specifically investigates how multiple alanine-to-valine substitutions (which each decrease the volume of the internal binding cavity by 38 A(3)) affect structure, stability, and anesthetic binding affinity of the four-alpha-helix bundles. Structure remains essentially unchanged when up to four alanine residues are changed to valine. However, stability increases as the number of these substitutions is increased. Anesthetic binding affinities are also... (More)
- Currently, it is thought that inhalational anesthetics cause anesthesia by binding to ligand-gated ion channels. This is being investigated using four-alpha-helix bundles, small water-soluble analogues of the transmembrane domains of the "natural" receptor proteins. The study presented here specifically investigates how multiple alanine-to-valine substitutions (which each decrease the volume of the internal binding cavity by 38 A(3)) affect structure, stability, and anesthetic binding affinity of the four-alpha-helix bundles. Structure remains essentially unchanged when up to four alanine residues are changed to valine. However, stability increases as the number of these substitutions is increased. Anesthetic binding affinities are also affected. Halothane binds to the four-alpha-helix bundle variants with 0, 1, and 2 substitutions with equivalent affinities but binds to the variants with 3 and 4 more tightly. The same order of binding affinities was observed for chloroform, although for a particular variant, chloroform was bound less tightly. The observed differences in binding affinities may be explained in terms of a modulation of van der Waals and hydrophobic interactions between ligand and receptor. These, in turn, could result from increased four-alpha-helix bundle binding cavity hydrophobicity, a decrease in cavity size, or improved ligand/receptor shape complementarity. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1127667
- author
- Manderson, Gavin LU ; Michalsky, Stuart J and Johansson, Jonas S.
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biochemistry
- volume
- 42
- issue
- 38
- pages
- 11203 - 11213
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:0141791264
- ISSN
- 0006-2960
- DOI
- 10.1021/bi034623b
- language
- English
- LU publication?
- yes
- 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
- a42c7064-c9d6-43fd-81cd-5bbe2f11ea65 (old id 1127667)
- date added to LUP
- 2016-04-01 12:21:00
- date last changed
- 2022-01-27 02:29:26
@article{a42c7064-c9d6-43fd-81cd-5bbe2f11ea65,
abstract = {{Currently, it is thought that inhalational anesthetics cause anesthesia by binding to ligand-gated ion channels. This is being investigated using four-alpha-helix bundles, small water-soluble analogues of the transmembrane domains of the "natural" receptor proteins. The study presented here specifically investigates how multiple alanine-to-valine substitutions (which each decrease the volume of the internal binding cavity by 38 A(3)) affect structure, stability, and anesthetic binding affinity of the four-alpha-helix bundles. Structure remains essentially unchanged when up to four alanine residues are changed to valine. However, stability increases as the number of these substitutions is increased. Anesthetic binding affinities are also affected. Halothane binds to the four-alpha-helix bundle variants with 0, 1, and 2 substitutions with equivalent affinities but binds to the variants with 3 and 4 more tightly. The same order of binding affinities was observed for chloroform, although for a particular variant, chloroform was bound less tightly. The observed differences in binding affinities may be explained in terms of a modulation of van der Waals and hydrophobic interactions between ligand and receptor. These, in turn, could result from increased four-alpha-helix bundle binding cavity hydrophobicity, a decrease in cavity size, or improved ligand/receptor shape complementarity.}},
author = {{Manderson, Gavin and Michalsky, Stuart J and Johansson, Jonas S.}},
issn = {{0006-2960}},
language = {{eng}},
number = {{38}},
pages = {{11203--11213}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Biochemistry}},
title = {{Effect of Four-alpha-Helix Bundle Cavity Size on Volatile Anesthetic Binding Energetics.}},
url = {{http://dx.doi.org/10.1021/bi034623b}},
doi = {{10.1021/bi034623b}},
volume = {{42}},
year = {{2003}},
}