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

Abstract:

: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.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Uppenberg J,Ohrner N,Norin M,Hult K,Kleywegt GJ,Patkar S,Waagen V,Anthonsen T,Jones TA

doi

10.1021/bi00051a035

subject

Has Abstract

pub_date

1995-12-26 00:00:00

pages

16838-51

issue

51

eissn

0006-2960

issn

1520-4995

journal_volume

34

pub_type

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