Surface Plasmon Resonance Reveals Nanomolar Affinity and Six Heme-Binding Motifs on Plasmin

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Summary of  International Journal of Biological Macromolecules https://doi.org/10.1016/j.ijbiomac.2026.154990
Dr. Isabeau Weyand et al.

Points

University of Koblenz researchers investigated how labile heme released during pathological red blood cell destruction interacts with the key fibrinolytic serine protease plasmin to influence blood clot dissolution.
Biophysical analyses including surface plasmon resonance and spectroscopy confirmed that plasmin exhibits nanomolar binding affinity and an overstoichiometric capacity for binding multiple labile heme molecules rapidly.
Systematic peptide mapping and molecular dynamics simulations successfully identified six discrete heme-binding motifs on plasmin with three surface-exposed sites displaying stable coordination near functional regions.
Experimental assays demonstrated that bound heme induces a pronounced concentration-dependent inhibition of plasmin-mediated fibrinolysis at pathological levels matching those found in severe hemolytic disease states.
These findings establish a crucial molecular framework connecting excess circulating heme directly to impaired blood clot breakdown and the elevated prothrombotic phenotypes observed in hemolytic disorders.

Summary

This study evaluated the molecular interaction between labile heme and the fibrinolytic enzyme plasmin to elucidate mechanisms underlying thrombosis in hemolytic disorders. Published in the International Journal of Biological Macromolecules by University of Koblenz researchers led by Prof. Dr. Marie-T. Hopp, the investigation addressed how red blood cell destruction influences the body’s ability to dissolve blood clots. Given that hemolytic conditions are clinically associated with an elevated risk of thrombosis, the research sought to determine whether free heme directly modulates plasmin function.

Using surface plasmon resonance and UV/visible spectroscopy, the biophysical analysis revealed that plasmin binds labile heme with high nanomolar affinity and demonstrates an overstoichiometric heme-binding capacity. Systematic mapping with plasmin-derived peptides, supported by molecular docking and molecular dynamics simulations, uncovered six discrete heme-binding motifs on the enzyme. Among these, three surface-exposed sites situated proximal to functional regions exhibited particularly stable coordination. Furthermore, experimental assays demonstrated that heme binding causes a pronounced, concentration-dependent inhibition of plasmin-mediated fibrinolysis at pathological heme levels.

The authors conclude that plasmin functions as a high-affinity heme-binding protease whose activity is impaired by excess circulating heme. By demonstrating that pathological hemolysis levels inhibit fibrinolysis through direct heme-plasmin interactions, these findings establish a novel molecular framework linking hemolytic disease to impaired clot dissolution and heightened prothrombotic risk.

Link to the article: https://www.sciencedirect.com/science/article/pii/S0141813026049421?via%3Dihub

References

Weyand, I., Arenz, L. A., Reddy, L. R., & Hopp, M.-T. (2026). Attenuation of fibrinolysis through heme binding to the serine protease plasmin. International Journal of Biological Macromolecules, 154990. https://doi.org/10.1016/j.ijbiomac.2026.154990