Professor Emeritus

Emil F. Pai

PhD, Universität Heidelberg

Medical Sciences Building
1 KIng's College Circle, Room 5318A, Toronto, Ontario Canada M5S 1A8
Research Interests
Structural Biology

Research Synopsis

Structure and Function of Proteins

Knowledge of the three-dimensional structure of a given protein is an absolutely essential prerequisite for the full understanding of the chemical basis of an enzyme’s catalytic mechanism, for interpreting the way structural proteins like e.g. actin interact with each other or how lead compounds have to be modified to improve affinity and specificity of drug candidates. In my lab, we use X-ray crystallographic techniques to establish the molecular architectures of proteins. We integrate our structural results with biochemical and molecular-biological as well as computational data, either collected in our laboratory or available through collaborations with specialists in the respective fields.

Our work is presently focussed on time-resolved crystallographic measurements of enzymatic activity. We are involved in the refinement of tools and techniques that allow data collection at predetermined time points after reaction initialization. We observed up to five full cycles of enzymatic catalysis and provided structural representation for reaction intermediates like the Michaelis-Menten complex, covalent intermediate and its hydrolysis, the ternary product complex and the free enzyme. We collaborated with chemists at the ETH Zurich on the synthesis of caged compounds that could be split by a laser pulse to produce the substrate molecule and with scientists at DESY in Hamburg on the design of chips and tools for data collection on dedicated synchrotron beamlines.

The lab is using these time-resolved crystallography techniques together with biochemical methods to investigate the chemistry underlying the enzymatic breakage of the carbon-fluorine bond, the most stable bond in organic chemistry. We hope to be able to contribute improvements to our knowledge of the detoxification of fluorinated compounds.

Recent Publications

P.W.Y. Chan, N. Chakrabarti, C. Ing, O. Halgas, T.K.W. To, M.A. Wälti, A.-P. Peptit, C. Tran, A. Savchenko, A.F. Yakunin, E.A. Edwards, R. Pomès & E.F. Pai
Defluorination capability of l-2-haloacid dehalogenases in the HAD-like hydrolase superfamily correlates with active site compactness.
ChemBioChem 10.1002/cbic.202100414 
doi: 10.1002/cbic.202100414

 P. Mehrabi#,*, R. Bückner, G. Bourenkov, H.M. Ginn, D. von Stetten, H.-M. Müller-Werkmei- ster, A. Kuo, T. Morizumi, B.T. Eger, W.-L. Ou, S. Oghbaey, A. Sarracini, J.E. Besaw, O. Pare´-Labrosse, S. Meier, H. Schikora, F. Tellkamp, A. Marx, D. Sherrell, D. Axford, R. Owen, O.P. Ernst, E.F. Pai, E.C. Schulz#,*, R.J.D. Miller (2021)
Serial femtosecond and serial synchrotron crystallography can yield data of equivalent quality: A systematic comparison.
Science Adv. 7(12): eabf1380.
doi: 10.1126/sciadv.abf1380; pre-print doi: 10.1101/2020.08.21.257170

P. Mehrabi#, E.C. Schulz#, R. Dsouza, H.M. Müller-Werkmeister, F. Tellkamp, R.J.D. Miller* & E.F. Pai* (2019)
Time-resolved crystallography reveals allosteric communication aligned with molecular breathing.
Science 365(6458): 1167-1170.
doi: 10.1126/science.aaw9904   PMID:31515393 

P. Mehrabi#, C. Di Pietroantonio#, T.H. Kim#, A. Slojka, K. Taverner, C. Ing, N. Kruglyak, R. Pomès, E.F. Pai* & R.S. Prosser* (2019)
Substrate-based allosteric regulation of a homodimeric enzyme.
J. Am. Chem. Soc. 141(29): 11540-11556.
doi: 10.1021/jacs.9b03703   PMID:31188575

E.C. Schulz#, P. Mehrabi#, H.M. Müller-Werkmeister#, F. Tellkamp, Ajay Iha, W. Stuart, E. Persch, R. De Gasparo, F. Diederich, E.F. Pai* & R.J.D. Miller* (2018)
The Hit-and-Return system enables efficient time-resolved serial synchrotron crystallography.
Nature Meth. 15:(11) 901-904.
doi: 10.1038/s41592-018-0180-2   PMID:30377366

T.H. Kim#, P. Mehrabi#, Z. Ren, A. Sljoka, C. Ing, A. Bezginov, L. Ye, R. Pomès, R.S. Prosser* & E.F. Pai* (2017) 
The role of dimer asymmetry and protomer dynamics in enzyme catalysis.
Science 355(6322): 262; eaag2355.
doi: 10.1126/science.aag2355   PMID:28104837