Conformational entropy changes upon lactose binding to the carbohydrate recognition domain of galectin-3.
Diehl, Carl LU ; Genheden, Samuel LU ; Modig, Kristofer LU
; Ryde, Ulf
LU
and Akke, Mikael
LU
(2009)
In Journal of Biomolecular NMR
45(1-2).
p.157-169
- Abstract
- The conformational entropy of proteins can make significant contributions to the free energy of ligand binding. NMR spin relaxation enables site-specific investigation of conformational entropy, via order parameters that parameterize local reorientational fluctuations of rank-2 tensors. Here we have probed the conformational entropy of lactose binding to the carbohydrate recognition domain of galectin-3 (Gal3), a protein that plays an important role in cell growth, cell differentiation, cell cycle regulation, and apoptosis, making it a potential target for therapeutic intervention in inflammation and cancer. We used (15)N spin relaxation experiments and molecular dynamics simulations to monitor the backbone amides and secondary amines of... (More)
- The conformational entropy of proteins can make significant contributions to the free energy of ligand binding. NMR spin relaxation enables site-specific investigation of conformational entropy, via order parameters that parameterize local reorientational fluctuations of rank-2 tensors. Here we have probed the conformational entropy of lactose binding to the carbohydrate recognition domain of galectin-3 (Gal3), a protein that plays an important role in cell growth, cell differentiation, cell cycle regulation, and apoptosis, making it a potential target for therapeutic intervention in inflammation and cancer. We used (15)N spin relaxation experiments and molecular dynamics simulations to monitor the backbone amides and secondary amines of the tryptophan and arginine side chains in the ligand-free and lactose-bound states of Gal3. Overall, we observe good agreement between the experimental and computed order parameters of the ligand-free and lactose-bound states. Thus, the (15)N spin relaxation data indicate that the molecular dynamics simulations provide reliable information on the conformational entropy of the binding process. The molecular dynamics simulations reveal a correlation between the simulated order parameters and residue-specific backbone entropy, re-emphasizing that order parameters provide useful estimates of local conformational entropy. The present results show that the protein backbone exhibits an increase in conformational entropy upon binding lactose, without any accompanying structural changes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1470232
- author
- Diehl, Carl
LU
; Genheden, Samuel
LU
; Modig, Kristofer
LU
; Ryde, Ulf
LU
and Akke, Mikael
LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biomolecular NMR
- volume
- 45
- issue
- 1-2
- pages
- 157 - 169
- publisher
- Springer
- external identifiers
-
- wos:000269079100014
- pmid:19641853
- scopus:69249220020
- ISSN
- 1573-5001
- DOI
- 10.1007/s10858-009-9356-5
- 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: Theoretical Chemistry (S) (011001039), Biophysical Chemistry (LTH) (011001011)
- id
- 666ecd0a-4c83-4611-a8a0-c498f83ec9d4 (old id 1470232)
- date added to LUP
- 2016-04-01 11:58:18
- date last changed
- 2023-04-18 21:19:38
@article{666ecd0a-4c83-4611-a8a0-c498f83ec9d4,
abstract = {{The conformational entropy of proteins can make significant contributions to the free energy of ligand binding. NMR spin relaxation enables site-specific investigation of conformational entropy, via order parameters that parameterize local reorientational fluctuations of rank-2 tensors. Here we have probed the conformational entropy of lactose binding to the carbohydrate recognition domain of galectin-3 (Gal3), a protein that plays an important role in cell growth, cell differentiation, cell cycle regulation, and apoptosis, making it a potential target for therapeutic intervention in inflammation and cancer. We used (15)N spin relaxation experiments and molecular dynamics simulations to monitor the backbone amides and secondary amines of the tryptophan and arginine side chains in the ligand-free and lactose-bound states of Gal3. Overall, we observe good agreement between the experimental and computed order parameters of the ligand-free and lactose-bound states. Thus, the (15)N spin relaxation data indicate that the molecular dynamics simulations provide reliable information on the conformational entropy of the binding process. The molecular dynamics simulations reveal a correlation between the simulated order parameters and residue-specific backbone entropy, re-emphasizing that order parameters provide useful estimates of local conformational entropy. The present results show that the protein backbone exhibits an increase in conformational entropy upon binding lactose, without any accompanying structural changes.}},
author = {{Diehl, Carl and Genheden, Samuel and Modig, Kristofer and Ryde, Ulf and Akke, Mikael}},
issn = {{1573-5001}},
language = {{eng}},
number = {{1-2}},
pages = {{157--169}},
publisher = {{Springer}},
series = {{Journal of Biomolecular NMR}},
title = {{Conformational entropy changes upon lactose binding to the carbohydrate recognition domain of galectin-3.}},
url = {{https://lup.lub.lu.se/search/files/136744136/126_akke1.pdf}},
doi = {{10.1007/s10858-009-9356-5}},
volume = {{45}},
year = {{2009}},
}