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We use X-ray crystallography to study the three-dimensional structures of proteins. The structural information is used for drug design, protein engineering, to understand catalytic mechanisms, and to explore protein evolution. Our main projects include studies of enzymes involved in purine and pyrimidine nucleotide metabolism, studies of enzymes involved in co-factor biosynthesis, especially thiamin and pyridoxal 5'-phosphate (PLP) biosynthesis, and enzymes involved in polyamine, purine, and pyrimidine and diphthamide biosynthesis.
Systematic investigation of an entire biochemical pathway provides important clues about protein evolution. Because of the role of purine and pyrimidine nucleotide metabolism and polyamines in diseases such as cancer and viral infection, many of the enzymes involved are targets for drug design. Many of the reactions catalyzed by enzymes in the co-factor biosynthesis pathways involve unprecedented chemistry and elucidation of catalytic mechanisms is a major goal. In addition, by studying these enzymes, we have also discovered interesting evolutionary links to other pathways. Please see our Group Webpage for additional information about our personnel, publications, and structures.
As Director of the Northeastern Collaborative Access Team (NE-CAT), we operate two undulator beamlines, both of which are capable of microdiffraction experiments, at Sector 24 of the Advanced Photon Source (APS) at Argonne National Laboratory in Argonne, Illinois. Please see NE-CAT for more information about this project.
principal investigator on
- AN UNDULATOR SOURCE FOR STRUCTURAL BIOLOGY awarded by NATL CTR FOR RESEARCH RESOURCES, NIH 2008 - 2013
- MEMORANDUM OF UNDERSTANDING awarded by NORTHEAST COLLABORATIVE ACCESS TEAM 2001 - 2012
- NRSA: A CHEMISTRY OF BIOLOGICAL SYSTEMS awarded by NATL INST OF GENERAL MEDICAL SCIENCES, NIH 2011 - 2016
- NRSA: CHEMISTRY OF BIOLOGICAL SYSTEMS: ARRA FUNDING awarded by NATL INST OF GENERAL MEDICAL SCIENCES, NIH 2009 - 2012
- STRUCTURAL BIOLOGY OF PURINE AND PYRIMIDINE BIOSYNTHESIS AND METABOLISM awarded by NATL INST OF HEALTH DHHS 2009 - 2013
- STRUCTURAL STUDIES OF ENZYMES OF THIAMIN BIOSYNTHESIS awarded by NATL INST OF HEALTH DHHS 2010 - 2014
co-principal investigator on
- X-ray crystallography of proteins; drug design; catalytic mechanisms; protein evolution; synchrotron radiation
- Toxoflavin Lyase Requires a Novel 1-His-2-Carboxylate Facial Triad. Biochemistry. 50:1091-1100. 2011
- Domain Organization in Candida Glabrata Thi6, a Bifunctional Enzyme Required for Thiamin Biosynthesis in Eukaryotes. Biochemistry. 49:9922-9934. 2010
- Structural and Mechanistic Studies on Klebsiella Pneumoniae 2-Oxo-4-Hydroxy-4-Carboxy-5-Ureidoimidazoline Decarboxylase. Journal of Biological Chemistry. 285:35446-35454. 2010
- HMP Binding Protein ThiY and HMP-P Synthase THI5 Are Structural Homologues. Biochemistry. 49:8929-8936. 2010
- Diphthamide Biosynthesis Requires an Organic Radical Generated by an Iron-Sulphur Enzyme. Nature. 465:891-896. 2010
- A maize thiamine auxotroph is defective in shoot meristem maintenance. The Plant Cell. 22:3305-3317. 2010
- The Structural and Biochemical Foundations of Thiamin Biosynthesis. Annual Review of Biochemistry. 78:569-603. 2009
- Reconstitution of ThiC in Thiamine Pyrimidine Biosynthesis Expands the Radical SAM Superfamily. Nature Chemical Biology. 4:715-772. 2008
- Structural Insights into the Mechanism of the PLP Synthase Holoenzyme from Thermotoga maritima. Biochemistry. 45:14559-14868. 2006
- The crystal structure of 5 '-deoxy-5 '-methylthioadenosine phosphorylase II from Sulfolobus solfataricus, a thermophilic enzyme stabilized by intramolecular disulfide bonds 2006
- Structural characterization of the regulatory proteins TenA and TenI from Bacillus subtilis and identification of TenA as a thiaminase II. Biochemistry. 44:2319-2329. 2005
- Crystal structure of an aminoimidazole riboside kinase from Salmonella enterica: Implications for the evolution of the ribokinase superfamily. Structure. 12:1809-1821. 2004
- Enzymatic reactions involving novel mechanisms of carbanion stabilization. Current Opinion in Chemical Biology. 8:508-515. 2004
- The Crystal Structure and Mechanism of Orotidine 5'-Monophosphate Decarboxylase. Proceedings of the National Academy of Sciences of the United States of America. 97:2005-2010. 2000
- Protein Crystallography Using a Multilayer Monochromator. Journal of Synchrotron Radiation. 5:494-496. 1998
- Macromolecular Crystallographic Results Obtained at CHESS Using a Detector Incorporating a Charge-Coupled Device. Review of Scientific Instruments. 66:1477-1479. 1995
selected publications listing
Zhang Y, Zhu X, Torelli AT, Lee M, Dzikovski B, Koralewski RM, Wang E, Freed J, Krebs C, Ealick SE, and Lin H. Diphthamide Biosynthesis Requires an Organic Radical Generated by an Iron-Sulphur Enzyme. Nature
French JB and Ealick SE. Structural and Mechanistic Studies on Klebsiella Pneumoniae 2-Oxo-4-Hydroxy-4-Carboxy-5-Ureidoimidazoline Decarboxylase. J. Biol. Chem . 285:35446-35454. (2010 ).
Bale S, Rajashankar KR, Perry K, Begley TP, and Ealick SE. HMP Binding Protein ThiY and HMP-P Synthase Thi5 Are Structural Homologues. Biochemistry 49:8929-8936 (2010 ).
Paul D, Chatterjee A, Begley TP, and Ealick SE. Domain Organization in Candida Glabrata Thi6, a Bifunctional Enzyme Required for Thiamin Biosynthesis in Eukaryotes. Biochemistry 49:9922-9934 (2010 ).
Fenwick MK, Philmus B, Begley T P, and Ealick SE. Toxoflavin Lyase Requires a Novel 1-His-2-Carboxylate Facial Triad, Biochemistry 50:1091-1100 (2011 ).
featured in archived article
PhD, University of Oklahoma, 1976
BS, Oklahoma State University, 1972
awards and distinctions listing
- Leukemia Society of America Special Fellow and Scholar Development Award
- Office of Naval Research Young Investigator
- Fellow of the American Association for the Advancement of Science
- 120 Baker Lab, Ithaca, NY 14853