UW team builds artificial enzyme

UW Chemistry professors Michael Gelb and Forrest Michael, in collaboration with Prof. David Baker (UW Biochemistry), have engineered an artificial enzyme capable of catalyzing a bimolecular Diels-Alder reaction with high stereoselectivity and substrate specificity. Their findings were reported July 16 in Science. The team of collaborators used computer modeling to screen over 10 billion possible protein backbone geometries for the ones that could support the right combination of active sites and catalytic residues. From this list, and further optimization, 84 de novo designs were selected for experimental work. Ultimately, two of the designed enzymes showed the ability to catalyze the Diels-Alder reaction.

The Diels-Alder reaction is one of the cornerstones of synthetic chemistry and no naturally occurring enzymes have been shown to catalyze it. Broader application of de novo enzyme design should be significantly useful in synthetic chemistry.

The authors of the paper also include Justin Siegel (graduate student in biochemistry, UW), Alexandre Zanghellini (graduate student in biochemistry, UW), Helena Lovick (graduate student in chemistry, UW), Gert Kiss (graduate student in chemistry, UCLA), Abigail Lambert (former graduate student with Prof. Stoddard), Jennifer St. Clair (Dept. of Biochemistry, UW), Jasmine Gallaher (lab technician, Baker lab),  Barry Stoddard (Professor at Fred Hutchinson Cancer Research Center in Seattle), Don Hilvert (Professor of Chemistry, ETH Zurich), Michael Gelb (Professor of Chemistry, UW), Ken Houk (Professor of Chemistry, UCLA), Forrest Michael (Associate Professor of Chemistry, UW), David Baker (Professor of Biochemistry, UW).

Picture: UW graduate student Justin Siegel, professor Forrest Michael, professor Michael Gelb and post-doctoral fellow Alexandre Zanghellini (Steve Ringman / The Seattle Times).

J. B. Siegel, A. Zanghellini, H. M. Lovick, G. Kiss, A. R. Lambert, J. L. St. Clair, J. L. Gallaher, D. Hilvert, M. H. Gelb, B. L. Stoddard, K. N. Houk, F. E. Michael, D. Baker “Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction”, Science, 2010, 239, 309-313

Read the Science paper

Read the article in The Seattle Times

Read the Chemistry World article

Also visit faculty webpages for Michael Gelb, Forrest Michael and David Baker.

Professor Michael Gelb Receives 2010 Hopkins Award

Professor Michael GelbProfessor Michael Gelb received the 2010 Hopkins Award on Friday May 19, delivering a lecture titled “Newborn Screening for Lysosomal Storage Diseases: Another Triumph for Organic Chemistry”. Lysosomal storage diseases are caused by a deficiency of enzymes that break down cellular metabolites. The Gelb group, in collaboration with Professors Frantisek Turecek and C. Ronald Scott (Pediatrics), has developed new methods based on synthetic organic chemistry and tandem mass spectrometry to screen newborns for several types of these often-fatal, but treatable, diseases.

 The Paul B. Hopkins Endowed Faculty Award is awarded to a member of the Department of Chemistry faculty to honor outstanding achievement in any area of professional responsibility. The award was established through an endowment from Emeritus Professor B. S. Rabinovitch.

For more information about Michael Gelb and his research, please visit his faculty page and research group website.

Chemistry department recognizes new graduates

Recent chemistry graduatesOn Friday June 11, in the Husky Union Building, nearly 1000 students and their friends and family gathered to honor students who received bachelors and Ph.D. degrees in chemistry and biochemistry. About 150 undergrads received graduation recognition certificates, as did about 15 Ph.D. recipients. The guest speaker for the ceremony was Dr. Susan Solomon of the National Oceanic and Atmospheric Administration in Boulder, Colorado. Dr. Solomon is a world-renowned atmospheric scientist, member of the National Academy of Sciences, and recipient of the National Medal of Science. She described some of the history of the Antarctic ozone hole, emphasizing the importance of individual contributors to the scientific enterprise.

Nearly 300 undergraduate students per year earn a bachelor’s degree in chemistry or biochemistry, making UW Chemistry the largest producer of these degrees in the U.S.

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Information about Dr. Susan Solomon