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Enrico Di Cera, M.D.

Alice A. Doisy Professor and Chairman
Biochemistry and Molecular Biology

Research

Structure, function and regulation of trypsin-like proteases and their zymogens, protein engineering, and allostery. A model of prothrombin bound to membrane highlighting the various conformational states of the protein. Di Cera JBC Cover – April 19 X-ray crystal structures of thrombin mutant Y225P in the E* (Protein Data Bank 3S7H), E (Protein Data Bank 3S7K), and E:L (Protein Data Bank 1THP) conformations (Vogt 2015). Each state represents a single conformation of prothrombin estimated from FRET measurements. X-ray crystal structure of ProTΔ146–167 in the Ca2+-bound form showing the arrangement of the various domains (Ac, A chain; Bc, B chain; GD, Gla domain; K1, kringle-1; K2, kringle-2) that are not vertically stacked (Pozzi 2014). Structural changes induced by Na_ binding to thrombin depicted by the structures of the Na+-free (1SGI, yellow) and Na+-bound (1SG8, cyan) forms (Page & Di Cera, 2006).

Select:

Role of Na+ and K+ in enzyme function.

Allostery in trypsin-like proteases suggests new therapeutic strategies.

Kinetic dissection of the pre-existing conformational equilibrium in the trypsin fold.

Crystal structure of prothrombin reveals conformational flexibility and mechanism of activation.

Site-specific analysis of mutational effects in proteins.

Research Interests

We are interested in the structure, function and engineering of trypsin-like proteases and their zymogen forms. The main focus of the lab is on thrombin and prothrombin as key components of the blood coagulation system. Our experimental approach includes kinetics, thermodynamics, site-directed mutagenesis, X-ray structural biology and single molecule spectroscopy.

Publications

Recent

Induced Fit Is a Special Case of Conformational Selection
Chakraborty P and Di Cera E
Pubmed | Biochemistry

Rational Design of Protein C Activators
Barranco-Medina S, Murphy M, Pelc L, Chen Z, Di Cera E and Pozzi N
Pubmed | Sci Rep

Costimulatory Effects of an Immunodominant Parasite Antigen Paradoxically Prevent Induction of Optimal CD8 T Cell Protective Immunity
Eickhoff CS, Zhang X, Vasconcelos JR, Motz RG, Sullivan NL, O’Shea K, Pozzi N, Gohara DW, Blase JR, Di Cera E and Hoft DF
Pubmed | PLoS Pathog.

Thrombin Cleavage of Plasmodium falciparum Erythrocyte Membrane Protein 1 Inhibits Cytoadherence
Gillrie MR, Renaux B, Russell-Goldman E, Avril M, Brazier AJ, Mihara K, Di Cera E, Milner DA, Hollenberg MD, Smith JD and Ho M
Pubmed | MBio

Molecular Mechanisms of Enzyme Activation by Monovalent Cations
Gohara DW and Di Cera E
Pubmed | J. Biol. Chem.