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Water dynamics in the large cavity of three lipid-binding proteins monitored by 17O magnetic relaxation dispersion.

Modig, Kristofer LU ; Rademacher, M; Lücke, C and Halle, Bertil LU (2003) In Journal of Molecular Biology 332(4). p.965-977
Abstract
Intracellular lipid-binding proteins contain a large binding cavity filled with water molecules. The role played by these water molecules in ligand binding is not well understood, but their energetic and dynamic properties must be important for protein function. Here, we use the magnetic relaxation dispersion (MRD) of the water 17O resonance to investigate the water molecules in the binding cavity of three different lipid-binding proteins: heart fatty acid-binding protein (H-FABP), ileal lipid-binding protein (I-LBP) and intestinal fatty acid-binding protein (I-FABP). Whereas about half of the crystallographically visible water molecules appear to be expelled by the ligand, we find that ligand binding actually increases the number of water... (More)
Intracellular lipid-binding proteins contain a large binding cavity filled with water molecules. The role played by these water molecules in ligand binding is not well understood, but their energetic and dynamic properties must be important for protein function. Here, we use the magnetic relaxation dispersion (MRD) of the water 17O resonance to investigate the water molecules in the binding cavity of three different lipid-binding proteins: heart fatty acid-binding protein (H-FABP), ileal lipid-binding protein (I-LBP) and intestinal fatty acid-binding protein (I-FABP). Whereas about half of the crystallographically visible water molecules appear to be expelled by the ligand, we find that ligand binding actually increases the number of water molecules within the cavity. At 300 K, the water molecules in the cavity exchange positions on a time-scale of about 1 ns and exchange with external water on longer time-scales (0.01–1 s). Exchange of water molecules among hydration sites within the cavity should be strongly coupled to ligand motion. Whereas a recent MD simulation indicates that the structure of the cavity water resembles a bulk water droplet, the present MRD results show that its dynamics is more than two orders of magnitude slower than in the bulk. These findings may have significant implications for the strength, specificity and kinetics of lipid binding. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Molecular Biology
volume
332
issue
4
pages
965 - 977
publisher
Elsevier
external identifiers
  • wos:000185399300018
  • pmid:12972265
  • scopus:0042827489
ISSN
1089-8638
DOI
10.1016/S0022-2836(03)00968-9
language
English
LU publication?
yes
id
b62cdf2b-b78a-4df7-ad5e-c1c0f6d79510 (old id 128090)
date added to LUP
2007-06-29 13:56:12
date last changed
2018-10-03 11:25:17
@article{b62cdf2b-b78a-4df7-ad5e-c1c0f6d79510,
  abstract     = {Intracellular lipid-binding proteins contain a large binding cavity filled with water molecules. The role played by these water molecules in ligand binding is not well understood, but their energetic and dynamic properties must be important for protein function. Here, we use the magnetic relaxation dispersion (MRD) of the water 17O resonance to investigate the water molecules in the binding cavity of three different lipid-binding proteins: heart fatty acid-binding protein (H-FABP), ileal lipid-binding protein (I-LBP) and intestinal fatty acid-binding protein (I-FABP). Whereas about half of the crystallographically visible water molecules appear to be expelled by the ligand, we find that ligand binding actually increases the number of water molecules within the cavity. At 300 K, the water molecules in the cavity exchange positions on a time-scale of about 1 ns and exchange with external water on longer time-scales (0.01–1 s). Exchange of water molecules among hydration sites within the cavity should be strongly coupled to ligand motion. Whereas a recent MD simulation indicates that the structure of the cavity water resembles a bulk water droplet, the present MRD results show that its dynamics is more than two orders of magnitude slower than in the bulk. These findings may have significant implications for the strength, specificity and kinetics of lipid binding.},
  author       = {Modig, Kristofer and Rademacher, M and Lücke, C and Halle, Bertil},
  issn         = {1089-8638},
  language     = {eng},
  number       = {4},
  pages        = {965--977},
  publisher    = {Elsevier},
  series       = {Journal of Molecular Biology},
  title        = {Water dynamics in the large cavity of three lipid-binding proteins monitored by 17O magnetic relaxation dispersion.},
  url          = {http://dx.doi.org/10.1016/S0022-2836(03)00968-9},
  volume       = {332},
  year         = {2003},
}