Computational design of an enzyme catalyst for a stereoselective bimolecular diels-alder reaction

Science

Volumn 329, Issue 5989, 2010, Pages 309-313

  Siegel, Justin B ^a,b,f   Zanghellini, Alexandre ^a,b,f   Lovick, Helena M ^b   Kiss, Gert ^c   Lambert, Abigail R ^d   St Clair, Jennifer L ^a   Gallaher, Jasmine L ^a   Hilvert, Donald ^e   Gelb, Michael H ^b   Stoddard, Barry L ^d   Houk, Kendall N ^c   Michael, Forrest E ^b   Baker, David ^a,b  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d Fred Hutchinson Cancer Research Center   (United States)

^e ETH ZURICH   (Switzerland)

^f Arzeda Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON; ENZYME;

CATALYSIS; CATALYST; CHEMICAL BONDING; CHEMICAL REACTION; CRYSTALLOGRAPHY; DESIGN; ENZYME ACTIVITY;

ARTICLE; BINDING SITE; CATALYST; CHEMICAL BOND; CYCLOADDITION; DIELS ALDER REACTION; ENZYME SPECIFICITY; MATHEMATICAL MODEL; PRIORITY JOURNAL; STEREOCHEMISTRY; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ACRYLAMIDES; ALGORITHMS; BUTADIENES; CARBON; CATALYSIS; CATALYTIC DOMAIN; COMPUTER SIMULATION; COMPUTER-AIDED DESIGN; CRYSTALLOGRAPHY, X-RAY; ENZYMES; HYDROGEN BONDING; HYDROPHOBICITY; KINETICS; MODELS, MOLECULAR; MUTAGENESIS; PHYSICOCHEMICAL PROCESSES; PROTEIN CONFORMATION; PROTEIN ENGINEERING; PROTEINS; SOFTWARE; STEREOISOMERISM; SUBSTRATE SPECIFICITY;

ALNUS;

EID: 77954811495     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1190239     Document Type: Article

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18. This work was supported by the Defense Advanced Research Projects Agency (DARPA), the Howard Hughes Medical Institute (HHMI), a Molecular Biophysics traineeship from the NIH for J.B.S., and the Lawrence Livermore National Laboratory Lawrence Scholars program for G.K. We thank M. Toscano (ETH) and C. Rosewall (University of Washington) for chemical synthesis and B. Siegel and Y.-h. Lam for helpful comments on the manuscript. The x-ray crystallographic coordinates have been deposited in the Protein Data Bank with accession ID 3I1C. The University of Washington has submitted a patent application on the protein sequence coding for the engineered enzymes reported here as well as some of the design methodology.