Home > Faculty

Gregory A. Petsko, D. Phil.
Professor of Biochemistry and Chemistry
Protein Crystallography
Gyula and Katica Tauber Professor of Biochemistry & Chemistry

Ph.D., Oxford University

contact information
(781) 736-4903

Petsko/Ringe Lab Home Page

My research is concerned with the three-dimensional structures of proteins and their biochemical functions. Most of my work is done in collaboration with Prof. Dagmar Ringe; we share facilities, students, and a number of projects. The tools used by our group are X-ray crystallography, molecular biology (especially site-directed mutagenesis), yeast genetics, organic synthesis, enzyme kinetics and molecular dynamics calculations. These methods are being applied to several general problems; the ones I am most involved with include: the structural basis for efficient enzymic catalysis of proton and hydride transfer; the role of the metal ions in bridged bimetalloenzyme active sites; direct visualization of proteins in action by time-resolved protein crystallography; the evolution of new enzyme activities from old ones; and the biology of the quiescent state in eukaryotic cells.

In some of these projects, we are trying to understand the structural basis for the catalytic power of the enzymes triose phosphate isomerase, xylose isomerase, mandelate racemase, aminopeptidase, mutarotase and ketosteroid isomerase. For all of them, structural information is being used to guide site-directed mutagenesis of the active site residues and combined quantum mechanics/molecular mechanics simulations of the catalytic reaction.

Protein crystallography is normally a static tool and cannot be used to follow biological reactions in real time. We have been involved in the development of new diffraction techniques, including Laue diffraction, that are capable of recording entire protein crystal data sets in a millisecond. When combined with low-temperature techniques, such methods can be used to determine the structures of catalytic intermediates.

A new area of research in the laboratory is the use of yeast genetics and biochemical techniques to study the quiscent state of eukaryotic cells. We have recently shown that cells arrest their cell cycle in G1 and then exit to the G0 state when unfolded proteins accumulate in the cytoplasm. Accompanying these cell cycle changes is a global shutdown in ribosomal protein expression. This process is partly under control of the heat shock transcription factor HSF. Another project that uses yeast genetics and molecular biology is our attempt to design a new metabolic pathway that will allow yeast to grow on lactonitrile or lactamide as sole carbon sources. The enzymes in this new pathway are being engineered from enzymes of the mandelonitrile pathway in bacteria by a combination of structure-directed and random mutagenesis.

Selected Publications:

Lieberman RL, Wustman BA, Huertas P, Powe AC Jr, Pine CW, Khanna R, Schlossmacher MG, Ringe D, Petsko GA. (2007) Structure of acid beta-glucosidase with pharmacological chaperone provides insight into Gaucher disease. Nat Chem Biol. 2007 Feb;3(2):101-107. [abstract]

Ding X, Rasmussen BF, Petsko GA, Ringe D. (2006) Direct crystallographic observation of an acyl-enzyme intermediate in the elastase-catalyzed hydrolysis of a peptidyl ester substrate: Exploiting the "glass transition" in protein dynamics. Bioorg Chem. 2006 Dec;34(6):410-23. [abstract]

Kraut DA, Sigala PA, Pybus B, Liu CW, Ringe D, Petsko GA, Herschlag D. (2006) Testing electrostatic complementarity in enzyme catalysis: hydrogen bonding in the ketosteroid isomerase oxyanion hole. PLoS Biol. 2006 Apr;4(4):e99.

Desmarais W, Bienvenue DL, Bzymek KP, Petsko GA, Ringe D, Holz RC. (2006) The high-resolution structures of the neutral and the low pH crystals of aminopeptidase from Aeromonas proteolytica. J Biol Inorg Chem. 2006 Jun;11(4):398-408. [abstract]

Das C, Hoang QQ, Kreinbring CA, Luchansky SJ, Meray RK, Ray SS, Lansbury PT, Ringe D, Petsko GA. (2006) Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4675-80. [abstract]

Mattos C, Bellamacina CR, Peisach E, Pereira A, Vitkup D, Petsko GA, Ringe D. (2006) Multiple solvent crystal structures: probing binding sites, plasticity and hydration. J Mol Biol. 2006 Apr 14;357(5):1471-82. [abstract]

Zhou W, Zhu M, Wilson MA, Petsko GA, Fink AL. (2006) The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein. J Mol Biol. 2006 Mar 3;356(4):1036-48. [abstract]

Wilson MA, Ringe D, Petsko GA. (2005) The atomic resolution crystal structure of the YajL (ThiJ) protein from Escherichia coli: a close prokaryotic homologue of the Parkinsonism-associated protein DJ-1. J Mol Biol. 2005 Oct 28;353(3):678-91. [abstract]

Bzymek KP, Moulin A, Swierczek SI, Ringe D, Petsko GA, Bennett B, Holz RC. (2005) Kinetic, spectroscopic, and X-ray crystallographic characterization of the functional E151H aminopeptidase from Aeromonas proteolytica. Biochemistry. 2005 Sep 13;44(36):12030-40. [abstract]

Liu D, Lepore BW, Petsko GA, Thomas PW, Stone EM, Fast W, Ringe D. (2005) Three-dimensional structure of the quorum-quenching N-acyl homoserine lactone hydrolase from Bacillus thuringiensis. Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11882-7. [abstract]

View Complete Publication List on PubMed: Gregory Petsko


Last update: February 6, 2007. E-mail comments or questions to the webmaster.