The role of ligand-gated conformational changes in enzyme catalysis
Moreira, Cátia ; Calixto, Ana Rita ; Richard, John P and Kamerlin, Shina Caroline Lynn LU
(2019)
In Biochemical Society Transactions
47(5).
p.1449-1460
- Abstract
Structural and biochemical studies on diverse enzymes have highlighted the importance of ligand-gated conformational changes in enzyme catalysis, where the intrinsic binding energy of the common phosphoryl group of their substrates is used to drive energetically unfavorable conformational changes in catalytic loops, from inactive open to catalytically competent closed conformations. However, computational studies have historically been unable to capture the activating role of these conformational changes. Here, we discuss recent experimental and computational studies, which can remarkably pinpoint the role of ligand-gated conformational changes in enzyme catalysis, even when not modeling the loop dynamics explicitly. Finally, through... (More)
Structural and biochemical studies on diverse enzymes have highlighted the importance of ligand-gated conformational changes in enzyme catalysis, where the intrinsic binding energy of the common phosphoryl group of their substrates is used to drive energetically unfavorable conformational changes in catalytic loops, from inactive open to catalytically competent closed conformations. However, computational studies have historically been unable to capture the activating role of these conformational changes. Here, we discuss recent experimental and computational studies, which can remarkably pinpoint the role of ligand-gated conformational changes in enzyme catalysis, even when not modeling the loop dynamics explicitly. Finally, through our joint analyses of these data, we demonstrate how the synergy between theory and experiment is crucial for furthering our understanding of enzyme catalysis.
(Less)
- author
- Moreira, Cátia
; Calixto, Ana Rita
; Richard, John P
and Kamerlin, Shina Caroline Lynn
LU
- publishing date
- 2019-10-31
- type
- Contribution to journal
- publication status
- published
- keywords
- Catalysis, Computer Simulation, Enzymes/metabolism, Ion Channel Gating, Ligands, Protein Conformation
- in
- Biochemical Society Transactions
- volume
- 47
- issue
- 5
- pages
- 12 pages
- publisher
- Portland Press
- external identifiers
-
- pmid:31657438
- scopus:85074378042
- ISSN
- 0300-5127
- DOI
- 10.1042/BST20190298
- language
- English
- LU publication?
- no
- additional info
- © 2019 The Author(s).
- id
- e6e84d65-58d8-4ff3-bc95-64fcd69cd26e
- date added to LUP
- 2025-01-11 20:14:50
- date last changed
- 2025-04-20 11:46:19
@article{e6e84d65-58d8-4ff3-bc95-64fcd69cd26e,
abstract = {{<p>Structural and biochemical studies on diverse enzymes have highlighted the importance of ligand-gated conformational changes in enzyme catalysis, where the intrinsic binding energy of the common phosphoryl group of their substrates is used to drive energetically unfavorable conformational changes in catalytic loops, from inactive open to catalytically competent closed conformations. However, computational studies have historically been unable to capture the activating role of these conformational changes. Here, we discuss recent experimental and computational studies, which can remarkably pinpoint the role of ligand-gated conformational changes in enzyme catalysis, even when not modeling the loop dynamics explicitly. Finally, through our joint analyses of these data, we demonstrate how the synergy between theory and experiment is crucial for furthering our understanding of enzyme catalysis.</p>}},
author = {{Moreira, Cátia and Calixto, Ana Rita and Richard, John P and Kamerlin, Shina Caroline Lynn}},
issn = {{0300-5127}},
keywords = {{Catalysis; Computer Simulation; Enzymes/metabolism; Ion Channel Gating; Ligands; Protein Conformation}},
language = {{eng}},
month = {{10}},
number = {{5}},
pages = {{1449--1460}},
publisher = {{Portland Press}},
series = {{Biochemical Society Transactions}},
title = {{The role of ligand-gated conformational changes in enzyme catalysis}},
url = {{http://dx.doi.org/10.1042/BST20190298}},
doi = {{10.1042/BST20190298}},
volume = {{47}},
year = {{2019}},
}