Abstract

Thrombin is a well characterized member of the serine protease family which is involved in the final steps of the blood coagulation pathway. Relative to the other members of the serine protease class of enzymes, thrombin has an unusual insertion at Leu60 which forms a rigid loop that partially occludes the active site. Ecotin is an E. coli serine protease inhibitor which interacts with a usually wide range of serine proteases of varied specificity. Wild type ecotin does not bind thrombin tightly and simple modeling experiments suggest that the thrombin 60s loop stericallyl prevents ecotin from binding. The ecotin mutant M84R interacts tightly with thrombin. The structure of the ecotin-thrombin complex will reveal how ecotin adapts to the drastic steric interference of the thrombin 60s loop to bind thrombin.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-17
Application #
5222779
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

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Lal, Neeraj K; Nagalakshmi, Ugrappa; Hurlburt, Nicholas K et al. (2018) The Receptor-like Cytoplasmic Kinase BIK1 Localizes to the Nucleus and Regulates Defense Hormone Expression during Plant Innate Immunity. Cell Host Microbe 23:485-497.e5
Pluvinage, Benjamin; Grondin, Julie M; Amundsen, Carolyn et al. (2018) Molecular basis of an agarose metabolic pathway acquired by a human intestinal symbiont. Nat Commun 9:1043
Beyerlein, Kenneth R; Jönsson, H Olof; Alonso-Mori, Roberto et al. (2018) Ultrafast nonthermal heating of water initiated by an X-ray Free-Electron Laser. Proc Natl Acad Sci U S A 115:5652-5657
Yoshizawa, Takuya; Ali, Rustam; Jiou, Jenny et al. (2018) Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites. Cell 173:693-705.e22
Hettle, Andrew; Fillo, Alexander; Abe, Kento et al. (2017) Properties of a family 56 carbohydrate-binding module and its role in the recognition and hydrolysis of ?-1,3-glucan. J Biol Chem 292:16955-16968
Oberthuer, Dominik; Knoška, Juraj; Wiedorn, Max O et al. (2017) Double-flow focused liquid injector for efficient serial femtosecond crystallography. Sci Rep 7:44628

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