Abstract
The catalytic triad of the neutral lipase from Humicola lanuginosa is buried by a short helix under aqueous conditions rendering the enzyme inactive. Upon adsorption to a lipid substrate interface this helix is displaced, thereby exposing the active site (interfacial activation). By covalently linking inhibitors to the active serine, it is possible to crystallize the enzyme in an interfacially activated state. Two such structures are reported here which mimic the tetrahedral transition states of lipolysis. To date, no crystal structures of a lipase--triglyceride complex exist for this enzyme. Therefore, possible interactions between this lipase and its substrate have been analysed through molecular modelling.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Carboxylic Ester Hydrolases / antagonists & inhibitors
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Carboxylic Ester Hydrolases / chemistry*
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Carboxylic Ester Hydrolases / metabolism
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Computer Simulation
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Crystallography, X-Ray
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Fatty Acids / chemistry
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Fatty Acids / metabolism
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Fungal Proteins / antagonists & inhibitors
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Fungal Proteins / chemistry*
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Fungal Proteins / metabolism
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Hydrolysis
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Mitosporic Fungi / enzymology*
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Models, Molecular
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Organophosphates / chemistry*
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Organophosphates / metabolism
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Substrate Specificity
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Triglycerides / chemistry
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Triglycerides / metabolism
Substances
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Fatty Acids
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Fungal Proteins
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Organophosphates
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Triglycerides
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dodecylethylphosphate
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diethyl phosphate
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Carboxylic Ester Hydrolases