Computational predictions of cysteine cathepsin-mediated fibrinogen proteolysis.

Abstract:

Fibrin clot formation is a proteolytic cascade of events with thrombin and plasmin identified as the main proteases cleaving fibrinogen precursor, and the fibrin polymer, respectively. Other proteases may be involved directly in fibrin(ogen) cleavage, clot formation, and resolution, or in the degradation of fibrin-based scaffolds emerging as useful tools for tissue engineered constructs. Here, cysteine cathepsins are investigated for their putative ability to hydrolyze fibrinogen, since they are potent proteases, first identified in lysosomal protein degradation and known to participate in extracellular proteolysis. To further explore this, we used two independent computational technqiues, molecular docking and bioinformatics sequence analysis (PACMANS), to predict potential binding interactions and sites of hydrolysis between cathepsins K, L, and S and fibrinogen. By comparing the results from these two objective, computational methods, it was determined that cathepsins K, L, and S do bind and cleave fibrinogen alpha, beta, and gamma chains at similar and unique sites. These differences were visualized experimentally by the unique cleaved fibrinogen banding patterns after incubation with each of the cathepsins, separately. In conclusion, human cysteine cathepsins K, L, and S are a new class of proteases that should be considered during fibrin(ogen) degradation studies both for disease processes where coagulation is a concern, and also in the implementation and design of bioengineered systems.

Profile Page: http://compmodelmatch.org/publications/6

PubMed ID: 29266558

Meetings: Finding Your Inner Modeler IV

Publication type: Journal

Journal: Protein Sci

Citation: Protein Sci. 2018 Mar;27(3):714-724. doi: 10.1002/pro.3366. Epub 2017 Dec 28.

Date Published: 22nd Dec 2017

Registered Mode: by PubMed ID

Authors: M. C. Ferrall-Fairbanks, D. M. West, S. A. Douglas, R. D. Averett, M. O. Platt

help Creator
Creators
Not specified
Submitter
Activity

Views: 110

Created: 5th Aug 2021 at 17:41

Related items

Powered by
(v.1.10.3)
Copyright © 2008 - 2020 The University of Manchester and HITS gGmbH
2019-2021 University of Connecticut