X-ray structure of Candida antarctica lipase a shows A novel lid structure and a likely mode of interfacial activation

Ericsson, Daniel J., Kasrayan, Alex, Johansson, Patrik, Bergfors, Terese, Sandstrom, Anders G., Backvall, Jan-E. and Mowbray, Sherry L. (2008) X-ray structure of Candida antarctica lipase a shows A novel lid structure and a likely mode of interfacial activation. Journal of Molecular Biology, 376 1: 109-119.


Author Ericsson, Daniel J.
Kasrayan, Alex
Johansson, Patrik
Bergfors, Terese
Sandstrom, Anders G.
Backvall, Jan-E.
Mowbray, Sherry L.
Title X-ray structure of Candida antarctica lipase a shows A novel lid structure and a likely mode of interfacial activation
Formatted title X-ray structure of Candida antarctica lipase a shows A novel lid structure and a likely mode of interfacial activation
Journal name Journal of Molecular Biology  (ERA 2012 Listed)    (ERA 2010 Rank A)   Check publisher's open access policy
Publication date 2008-02
Sub-type Article
DOI 10.1016/j.jmb.2007.10.079
Volume number 376
Issue number 1
ISSN 0022-2836
1089-8638
Start page 109
End page 119
Total pages 11
Place of publication London, United Kingdom
Publisher Academic Press
Language eng
Formatted abstract In nature, lipases (EC 3.1.1.3) catalyze the hydrolysis of triglycerides to form glycerol and fatty acids. Under the appropriate conditions, the reaction is reversible, and so biotechnological applications commonly make use of their capacity for esterification as well as for hydrolysis of a wide variety of compounds. In the present paper, we report the X-ray structure of lipase A from Candida antarctica, solved by single isomorphous replacement with anomalous scattering, and refined to 2.2-Å resolution. The structure is the first from a novel family of lipases. Contrary to previous predictions, the fold includes a well-defined lid as well as a classic α/β hydrolase domain. The catalytic triad is identified as Ser184, Asp334 and His366, which follow the sequential order considered to be characteristic of lipases; the serine lies within a typical nucleophilic elbow. Computer docking studies, as well as comparisons to related structures, place the carboxylate group of a fatty acid product near the serine nucleophile, with the long lipid tail closely following the path through the lid that is marked by a fortuitously bound molecule of polyethylene glycol. For an ester substrate to bind in an equivalent fashion, loop movements near Phe431 will be required, suggesting the primary focus of the conformational changes required for interfacial activation. Such movements will provide virtually unlimited access to solvent for the alcohol moiety of an ester substrate. The structure thus provides a basis for understanding the enzyme's preference for acyl moieties with long, straight tails, and for its highly promiscuous acceptance of widely different alcohol and amine moieties. An unconventional oxyanion hole is observed in the present structure, although the situation may change during interfacial activation.
Keyword lipase
interfacial activation
hydrolase
X-ray structure
substrate specificity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article
Collections: ERA 2012 Admin Only
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 48 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 46 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Access Statistics: 55 Abstract Views  -  Detailed Statistics
Created: Wed, 12 Oct 2011, 17:40:39 EST by System User on behalf of School of Chemistry & Molecular Biosciences