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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2010-3-5
pubmed:abstractText
We studied the inhibitory effects of trifluoroethanol (TFE) on the activity and conformation of tyrosinase. TFE increased the degree of secondary structure of tyrosinase, which directly resulted in enzyme inactivation. A reciprocal study showed that TFE inhibited tyrosinase in a slope-parabolic mixed-type inhibition manner (K (I) = 0.5 +/- 0.096 M). Time-interval kinetic studies showed that the inhibition was best described as first order with biphasic processes. Intrinsic and 1-anilinonaphthalene-8-sulfonate-binding fluorescences were also measured to gain more insight into the supposed structural changes; these showed that TFE induced a conspicuous tertiary structural change in tyrosinase by exposing hydrophobic surfaces. We also predicted the tertiary structure of tyrosinase and simulated its docking with TFE. The docking simulation was successful with significant scores (binding energy for Autodock4 = -4.75 kcal/mol; for Dock6 = -23.07 kcal/mol) and suggested that the TRP173 residue was mainly responsible for the interaction with TFE. Our results provide insight into the structure of tyrosinase and allow us to describe a new inhibition strategy that works by inducing conformational changes rather than targeting the active site of the protein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1559-0291
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
160
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1896-908
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The effect of trifluoroethanol on tyrosinase activity and conformation: inhibition kinetics and computational simulations.
pubmed:affiliation
Department of Environmental Health, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't