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A structural view of evolutionary divergence Ben Spiller*, Anne Gershenson, Frances H. Arnold, and Raymond C. Stevens
 

Summary: A structural view of evolutionary divergence
Ben Spiller*, Anne Gershenson, Frances H. Arnold, and Raymond C. Stevens§¶
*Department of Molecular and Cell Biology, University of California, Berkeley, CA 92037; Materials Science Division, Lawrence Berkeley National
Laboratory, Berkeley CA 94720; Division of Chemistry and Chemical Engineering, 210-41, California Institute of Technology, Pasadena, CA 91125; and
§Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037
Communicated by William N. Lipscomb, Harvard University, Cambridge, MA, August 30, 1999 (received for review July 2, 1999)
Two directed evolution experiments on p-nitrobenzyl esterase
yielded one enzyme with a 100-fold increased activity in aqueous-
organic solvents and another with a 17°C increase in thermosta-
bility. Structures of the wild type and its organophilic and ther-
mophilic counterparts are presented at resolutions of 1.5 Ĺ, 1.6 Ĺ,
and 2.0 Ĺ, respectively. These structures identify groups of inter-
acting mutations and demonstrate how directed evolution can
traverse complex fitness landscapes. Early-generation mutations
stabilize flexible loops not visible in the wild-type structure and set
the stage for further beneficial mutations in later generations. The
mutations exert their influence on the esterase structure over large
distances, in a manner that would be difficult to predict. The loops
with the largest structural changes generally are not the sites of
mutations. Similarly, none of the seven amino acid substitutions in

  

Source: Arnold, Frances H. - Division of Chemistry and Chemical Engineering, California Institute of Technology

 

Collections: Chemistry; Biology and Medicine