Our research builds upon 30+ years of continuously funded work on the enzymology and structural biology of proteins involved in blood coagulation and on mechanisms of ligand binding.
We are interested in the structural enzymology of proteins responsible for blood coagulation, with the goal of unraveling their molecular architecture and mechanisms. Our approach uses a combination of conventional (rapid kinetics, protein engineering, X-ray crystallography) and innovative (smFRET, cryo-EM) biophysical techniques.
We currently focus on the structure, function and regulation of prothrombin (HL049413), protein C (HL139554) and factor V (HL147821). Also of interest is the molecular basis of protease specificity.
Cryo-EM structures of human coagulation factors V and Va. Ruben EA, Rau MJ, Fitzpatrick JAJ, Di Cera E. Blood 137(22):3137, 2021.
Cryo-EM structure of the prothrombin-prothrombinase complex. Ruben EA, Summers B, Rau MJ, Fitzpatrick JAJ, Di Cera E. Blood 139(24):3463, 2022.
Selected Reviews and Commentaries
- 1. Defining epitopes: it is not as easy as it seems. Greenspan NP, Di Cera E. (1999) Nat Biotechnol 17, 936-937.
- 2. Evolution of enzyme cascades from embryonic development to blood coagulation. Krem MM, Di Cera E. (2002) Trends Biochem Sci 26, 67-74.
- 3. A structural perspective on enzymes activated by monovalent cations. Di Cera E. (2006) J Biol Chem 281, 1305-1308.
- 4. Role of Na+ and K+ in enzyme function. Page MJ, Di Cera E. (2006) Physiol Rev 86, 1049-1092.
- 5. Serine peptidases: classification, structure and function. Page MJ, Di Cera E. (2008) Cell Mol Life Sci 65, 1220-1236.
- 6. Thrombin. Di Cera E. (2008) Mol Aspects Med 29, 203-254
- 7. Engineering protease specificity made simple, but not simpler. Di Cera E. (2008) Nat Chem Biol 4, 270-271.
- 8. Mechanisms of ligand binding. Di Cera E. (2020) Biophys Rev 1, 011303.
Selected Publications (past 5 years)
Structural Biology
- 1. Cryo-EM structures of human coagulation factors V and Va. Ruben EA, Rau MJ, Fitzpatrick JAJ, Di Cera E (2021) Blood 137, 3137-3144. See Ahnström (2021) Blood 137, 3011-3013 for a commentary.
- 2. Cryo-EM structure of the prothrombin-prothrombinase complex. Ruben EA, Summers B, Rau MJ, Fitzpatrick JAJ, Di Cera E (2022) Blood 139, 3463-3473. See Spiegel (2022) Blood, 139, 3451-3453 for a commentary.
- 3. Cryo-EM structure of coagulation factor V short. Mohammed BM, Pelc LA, Rau MJ, Di Cera E (2023) Blood 141, 3215-3225. See Castoldi (2023) Blood, 141, 3134-3135 for a commentary.
- 4. Structural architecture of the acidic region of the B domain of coagulation factor V. Mohammed BM, Basore K, Summers B, Pelc LA, Di Cera E (2024) J Thromb Haemost 22, 709-714.
- 5. The prothrombin-prothrombinase interaction. Stojanovski BM, Mohammed BM, Di Cera E (2024) Subcell Biochem 104, 409-423.
- 6. Cryo-EM structure of coagulation factor Va bound to activated protein C. Mohammed BM, Basore K, Di Cera E (2025) Blood, submitted for publication.
Enzymology
- 1. Role of sequence and position of the cleavage sites in prothrombin activation. Stojanovski BM, Di Cera E (2021) J Biol Chem 297, 100955.
- 2. The active site region plays a critical role in Na+ binding to thrombin. Pelc LA, Koester SK, Kukla CR, Chen Z, Di Cera E (2022) J Biol Chem 298, 101458.
- 3. Monitoring prothrombin activation in plasma through loss of FRET. Stojanovski BM, Di Cera E (2023) J Thromb Haemost 21, 1769-1778.
- 4. Thrombin has dual trypsin-like and chymotrypsin-like specificity. Stojanovski BM, Pelc LA, Di Cera E (2024) J Thromb Haemost 22, 1009-1015.
- 5. Conformation of factor Xa in solution revealed by single molecular spectroscopy. Stojanovski BM, Di Cera E (2024) J Thromb Haemost 22, 2767-2772.
- 6. Replacement of a single residue changes the primary specificity of thrombin. Dei Rossi A, Deavila S, Mohammed BM, Korolev S, Di Cera E (2025) J Thromb Haemost Jan 3 [epub ahead of print].
Complete Bibliography via PubMed: Di Cera E