Determinants of specificity in coagulation proteases

Proteases play diverse roles in a variety of essential biological processes, both as non-specific catalysts of protein degradation and as highly specific agents that control physiologic events. Here, we review the mechanisms of substrate specificity employed by serine proteases and focus our discussion on coagulation proteases. We dissect the interplay between active site and exosite specificity and how substrate recognition is regulated allosterically by Na+ binding. We also draw attention to a functional polarity that exists in the serine protease fold, which sheds light on the structural linkages between the active site and exosites.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

This review examines substrate specificity in serine proteases with a focus on coagulation proteases. It dissects how active-site and exosite specificity interact and how Na+ binding allosterically regulates substrate recognition, highlighting a functional polarity within the protease fold.

Explore how this research connects to clinical practice

More peer-reviewed studies in Drug Development.

• Hirudotherapy in Medicine and Dentistry — Jha K et al. (2015)
• Leech therapy: a history — Hyson J (2005)
• Hirudins of the Asian medicinal leech, Hirudinaria manillensis: same same, but different — Lukas P et al. (2019)
• Transcriptomic analysis of the salivary gland of medicinal leech Hirudo nipponia — Lu Z et al. (2018)
• Molecular dynamic and pharmacological studies on protein-engineered hirudin variants of Hirudinaria manillensis and Hirudo medicinalis — Sun Y et al. (2022)
• Cell-free synthesis of the hirudin variant 1 of the blood-sucking leech Hirudo medicinalis — Wüstenhagen D et al. (2020)
• Hirudin variants production by genetic engineered microbial factory — Zhang J, Lan N (2018)
• Hirudin in heparin-induced thrombocytopenia — Lubenow N, Greinacher A (2002)
• Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis — Han J et al. (2023)
• Hirudin as alternative anticoagulant--a historical review — Markwardt F (2002)

Browse all ASH-analysed research →