Crystallographic and molecular-modeling studies of lipase B from Candida antarctica reveal a stereospecificity pocket for secondary alcohols

Many lipases are potent catalysts of stereoselective reactions and are therefore of interest for use in chemical synthesis. The crystal structures of lipases show a large variation in the shapes of their active site environments that may explain the large variation in substrate specificity of these...

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Bibliographic Details
Published in:Biochemistry (Easton) 1995-12, Vol.34 (51), p.16838-16851
Main Authors: Uppenberg, Jonas, Oehrner, Niklas, Norin, Martin, Hult, Karl, Kleywegt, Gerard J, Patkar, Shamkant, Waagen, Viggo, Anthonsen, Thorleif, Jones, T. Alwyn
Format: Article
Language:English
Subjects:
Alcohols - chemistry
Alcohols - metabolism
Alcohols/chemistry/metabolism
Binding Sites
Candida - enzymology
Candida antarctica
Crystallography, X-Ray
Enzyme Inhibitors - pharmacology
Lipase - antagonists & inhibitors
Lipase - chemistry
Lipase - metabolism
Lipase/antagonists & inhibitors/chemistry/metabolism
Models, Molecular
Organophosphonates - pharmacology
Phosphonic Acids/pharmacology
Polysorbates
Protein Conformation
Stereoisomerism
Substrate Specificity
Thermodynamics
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Summary:Many lipases are potent catalysts of stereoselective reactions and are therefore of interest for use in chemical synthesis. The crystal structures of lipases show a large variation in the shapes of their active site environments that may explain the large variation in substrate specificity of these enzymes. We have determined the three-dimensional structure of Candida antarctica lipase B (CALB) cocrystallized with the detergent Tween 80. In another crystal form, the structure of the enzyme in complex with a covalently bound phosphonate inhibitor has been determined. In both structures, the active site is exposed to the external solvent. The potential lid-forming helix alpha 5 in CALB is well-ordered in the Tween 80 structure and disordered in the inhibitor complex. The tetrahedral intermediates of two chiral substrates have been modeled on the basis of available structural and biochemical information. The results of this study provide a structural explanation for the high stereoselectivity of CALB toward many secondary alcohols.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00051a035