Enrico Di Cera, M.D.
Alice A. Doisy Professor and Chairman

Structural enzymology of coagulation factors.

Office: DRC 533
Voice: (314) 977-9201

Research Interests

We are interested in the interaction of prothrombin with prothrombinase leading to generation of thrombin and blood clotting, and the interaction of the thrombin-thrombomodulin complex with protein C initiating the negative feed-back loop that shuts down the coagulation response. Our experimental approach merges classical enzymology and X-ray structural biology with innovative techniques like smFRET, 19F NMR and Cryo-EM.
Research Highlights

A paper in Blood entitled “Cryo-EM structures of human coagulation factors V and Va” details work on solving the structures of factor V and Va. Factor V is the precursor to factor Va, which combines with calcium and phospholipids to activate prothrombin in the coagulation cascade.

Cryo-EM was used to uncover the structures, including revealing the proteolytic processing sites and epitope binding sites. Key differences between the two structures were revealed and helped to clarify the function of these factors in coagulation.

Di Cera Graphical Abstract-domain labels
Prothrombin-Prothrombinase Complex

A plenary paper in Blood entitled “Cryo-EM structure of the prothrombin-prothrombinase complex” details the spatial arrangement of the structure of the prothrombin-fXa-fVa complex for the first time and offers a molecular view of prothrombin activation along the meizothrombin pathway.

Researchers used Cryo-EM to solve the structures of the fVa-fXa complex, one free on nanodiscs and the other bound to prothrombin.

Visual Abstract

Video showing the complex of prothrombin (yellow), fVa (green), and fXa (red).

Recent Publications

Department of Biochemistry and Molecular Biology