2009
DOI: 10.1016/j.jmb.2009.06.076
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Pathways and Mechanisms for Product Release in the Engineered Haloalkane Dehalogenases Explored Using Classical and Random Acceleration Molecular Dynamics Simulations

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Cited by 98 publications
(100 citation statements)
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References 93 publications
(171 reference statements)
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“…In most cases, the product release and substrate access share the same tunnel in proteins (31)(32)(33). However, the product-release tunnel in enzymes such as haloalkane dehalogenases is distinct from the substrate access tunnel, which sometimes makes the product release step a rate-limiting bottleneck, thereby providing a new target for efficient protein engineering (34)(35)(36). Previously, there was no report of an independent product-release site in EHs.…”
Section: Discussionmentioning
confidence: 99%
“…In most cases, the product release and substrate access share the same tunnel in proteins (31)(32)(33). However, the product-release tunnel in enzymes such as haloalkane dehalogenases is distinct from the substrate access tunnel, which sometimes makes the product release step a rate-limiting bottleneck, thereby providing a new target for efficient protein engineering (34)(35)(36). Previously, there was no report of an independent product-release site in EHs.…”
Section: Discussionmentioning
confidence: 99%
“…Several experimental and computational studies of enzymes with buried active sites, such as acetylcholinesterases (6,44), haloalkane dehalogenases (12,43), cytochromes P450 (7,18,45,46), and lipases (47)(48)(49)(50) have been performed and have underlined the importance of enzyme tunnels for catalytic activity, specificity, and enantioselectivity. Here, we report the first combined experimental and computational study of the effect of a tunnel-lining mutation on the mechanism of the biotechnologically interesting enzyme, haloalkane dehalogenase LinB.…”
Section: Discussionmentioning
confidence: 99%
“…Considering that ligand binding is a reversible process, this method can be used to explore substrate dissociation and binding pathways as well (19). The RAMD method has been successfully employed to study ligand dissociation paths in cytochrome P450 (19), rhodopsin (22), haloalkane dehalogenase (23), histone deacetylase (24), heme oxygenase (25), thyroid hormone receptor (26), P-glycoprotein (27), and B-RAF kinase (28), among many others.…”
mentioning
confidence: 99%