Outputs (9)

Structures of factor XI and prekallikrein bound to domain 6 of high–molecular weight kininogen reveal alternate domain 6 conformations and exosites (2023)
Journal Article
Li, C., Barroeta, A. B., Wong, S. S., Kim, H. J., Pathak, M., Dreveny, I., …Emsley, J. (2023). Structures of factor XI and prekallikrein bound to domain 6 of high–molecular weight kininogen reveal alternate domain 6 conformations and exosites. Journal of Thrombosis and Haemostasis, https://doi.org/10.1016/j.jtha.2023.03.042

Background: High–molecular weight kininogen (HK) circulates in plasma as a complex with zymogen prekallikrein (PK). HK is both a substrate and a cofactor for activated plasma kallikrein, and the principal exosite interactions occur between PK N-termi... Read More about Structures of factor XI and prekallikrein bound to domain 6 of high–molecular weight kininogen reveal alternate domain 6 conformations and exosites.

Crystal structure and substrate-induced activation of ADAMTS13 (2019)
Journal Article
Petri, A., Kim, H. J., Xu, Y., de Groot, R., Li, C., Vandenbulcke, A., …Crawley, J. T. (2019). Crystal structure and substrate-induced activation of ADAMTS13. Nature Communications, 10, Article 3781. https://doi.org/10.1038/s41467-019-11474-5

Platelet recruitment to sites of blood vessel damage is highly dependent upon von Willebrand factor (VWF). VWF platelet-tethering function is proteolytically regulated by the metalloprotease ADAMTS13. Proteolysis depends upon shear-induced conformati... Read More about Crystal structure and substrate-induced activation of ADAMTS13.

Crystal structures of the recombinant β-factor XIIa protease with bound Thr-Arg and Pro-Arg substrate mimetics (2019)
Journal Article
Pathak, M., Manna, R., Li, C., Kaira, B. G., Hamad, B. K., Belviso, B. D., …Emsley, J. (2019). Crystal structures of the recombinant β-factor XIIa protease with bound Thr-Arg and Pro-Arg substrate mimetics. Acta Crystallographica. Section d, Structural Biology, 75(6), 578-591. https://doi.org/10.1107/s2059798319006910

© 2019 International Union of Crystallography. Coagulation factor XII (FXII) is a key initiator of the contact pathway, which contributes to inflammatory pathways. FXII circulates as a zymogen, which when auto-activated forms factor XIIa (FXIIa). Her... Read More about Crystal structures of the recombinant β-factor XIIa protease with bound Thr-Arg and Pro-Arg substrate mimetics.

Plasma kallikrein structure reveals apple domain disc rotated conformation compared to factor XI (2019)
Journal Article
Li, C., Voos, K. M., Pathak, M., Hall, G., McCrae, K. R., Dreveny, I., …Emsley, J. (2019). Plasma kallikrein structure reveals apple domain disc rotated conformation compared to factor XI. Journal of Thrombosis and Haemostasis, 17(5), 759-770. https://doi.org/10.1111/jth.14418

Background Plasma prekallikrein (PK) and factor XI (FXI) are apple domain‐containing serine proteases that when activated to PKa and FXIa cleave substrates kininogen, factor XII, and factor IX, respectively, directing plasma coagulation, bradykinin... Read More about Plasma kallikrein structure reveals apple domain disc rotated conformation compared to factor XI.

A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain (2016)
Journal Article
Wong, S. S., Østergaard, S., Hall, G., Li, C., Williams, P. M., Stennicke, H., & Emsley, J. (in press). A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain. Blood, 127(23), https://doi.org/10.1182/blood-2015-10-676122

Factor XI (FXI) is the zymogen of FXIa, which cleaves FIX in the intrinsic pathway of coagulation. FXI is known to exist as a dimer and interacts with multiple proteins via its 4 apple domains in the “saucer section” of the enzyme; however, to date,... Read More about A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain.

PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism (2016)
Journal Article
Drees, S. L., Li, C., Prasetya, F., Saleem, M., Dreveny, I., Williams, P., …Fetzner, S. (2016). PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism. Journal of Biological Chemistry, 291(13), https://doi.org/10.1074/jbc.M115.708453

Pseudomonas aeruginosa produces a number of alkylquinolone-type secondary metabolites best known for their antimicrobial effects and involvement in cell-cell communication. In the alkylquinolone biosynthetic pathway, the β-ketoacyl-(acyl carrier prot... Read More about PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism.

Coagulation factor XII protease domain crystal structure (2015)
Journal Article
Pathak, M., Wilmann, P., Awford, J., Li, C., Hamad, B., Fischer, P., …Emsley, J. (2015). Coagulation factor XII protease domain crystal structure. Journal of Thrombosis and Haemostasis, 13(4), 580-591. https://doi.org/10.1111/jth.12849

Background: Coagulation factor XII is a serine protease that is important for kinin generation and blood coagulation, cleaving the substrates plasma kallikrein and FXI. Objective: To investigate FXII zymogen activation and substrate recognition by d... Read More about Coagulation factor XII protease domain crystal structure.

Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction (2014)
Journal Article
Reddy, T. R., Li, C., Guo, X., Fischer, P. M., & Dekker, L. V. (2014). Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction. Bioorganic and Medicinal Chemistry, 22(19), 5378-5391. https://doi.org/10.1016/j.bmc.2014.07.043

Recent target validation studies have shown that inhibition of the protein interaction between annexin A2 and the S100A10 protein may have potential therapeutic benefits in cancer. Virtual screening identified certain 3,4,5-trisubstituted 4H-1,2,4-tr... Read More about Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction.

Three-dimensional pharmacophore design and biochemical screening identifies substituted 1,2,4-triazoles as inhibitors of the annexin A2-S100A10 protein interaction (2012)
Journal Article
Reddy, T. R., Li, C., Fischer, P. M., & Dekker, L. V. (2012). Three-dimensional pharmacophore design and biochemical screening identifies substituted 1,2,4-triazoles as inhibitors of the annexin A2-S100A10 protein interaction. ChemMedChem, 7(8), https://doi.org/10.1002/cmdc.201200107

Protein interactions are increasingly appreciated as targets in small-molecule drug discovery. The interaction between the adapter protein S100A10 and its binding partner annexin A2 is a potentially important drug target. To obtain small-molecule sta... Read More about Three-dimensional pharmacophore design and biochemical screening identifies substituted 1,2,4-triazoles as inhibitors of the annexin A2-S100A10 protein interaction.