ArticleThe EMBO journal2000
Crystal structure of the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor.
Article in The EMBO journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 77 citations in OpenAlex.
- Mechanisms and research progress of insect-derived medicines in intervention for ischemic stroke.IBRO neuroscience reports · 2025Review
- Identification and functional characterization of multiple haemadins and an oligomeric decorsin in the Asian land leech Haemadipsa interrupta.Parasitology research · 2024Article
- Aptameric hirudins as selective and reversible EXosite-ACTive site (EXACT) inhibitors.Nature communications · 2024Article
- From haemadin to haemanorm: Synthesis and characterization of full-length haemadin from the leech Haemadipsa sylvestris and of a novel bivalent, highly potent thrombin inhibitor (haemanorm).Protein science : a publication of the Protein Society · 2023Article
- Make it double: identification and characterization of a Tandem-Hirudin from the Asian medicinal leech Hirudinaria manillensis.Parasitology research · 2022Article
- Screening of the Promising Direct Thrombin Inhibitors from Haematophagous Organisms. Part I: Recombinant Analogues and Their Antithrombotic Activity In Vitro.Biomedicines · 2021Article
- Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands.International journal of molecular sciences · 2021Review
- Tyrosine sulfation modulates activity of tick-derived thrombin inhibitors.Nature chemistry · 2017Article
- High-resolution structure of a Kazal-type serine protease inhibitor from the dengue vector Aedes aegypti.Acta crystallographica. Section F, Structural biology communications · 2017Article
- Phosphorylation of the regulatory light chain of myosin in striated muscle: methodological perspectives.European biophysics journal : EBJ · 2016Review
- More than just one: multiplicity of Hirudins and Hirudin-like Factors in the Medicinal Leech, Hirudo medicinalis.Molecular genetics and genomics : MGG · 2016Article
- Identification and Mechanistic Analysis of a Novel Tick-Derived Inhibitor of Thrombin.PloS one · 2015Article
- On scaffold hopping: challenges in the discovery of sulfated small molecules as mimetics of glycosaminoglycans.Bioorganic & medicinal chemistry letters · 2013Article
- Unique thrombin inhibition mechanism by anophelin, an anticoagulant from the malaria vector.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Crystallization and preliminary crystallographic characterization of the N-terminal Kunitz domain of boophilin.Acta crystallographica. Section F, Structural biology and crystallization communications · 2012Article
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- Crystallization and preliminary crystallographic characterization of three peptidic inhibitors in complex with α-thrombin.Acta crystallographica. Section F, Structural biology and crystallization communications · 2011Article
- Sulfated, low-molecular-weight lignins are potent inhibitorsof plasmin, in addition to thrombin and factor Xa: Novel opportunity for controlling complex pathologies.Thrombosis and haemostasis · 2010Article
- Fibrinogen-elongated gamma chain inhibits thrombin-induced platelet response, hindering the interaction with different receptors.The Journal of biological chemistry · 2008Article
- Article
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8 authors at 1 institution in 1 country.
Funding
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Abstract
The serine proteinase alpha-thrombin plays a pivotal role in the regulation of blood fluidity, and therefore constitutes a primary target in the treatment of various haemostatic disorders. Haemadin is a slow tight- binding thrombin inhibitor from the land-living leech Haemadipsa sylvestris. Here we present the 3.1 A crystal structure of the human alpha-thrombin- haemadin complex. The N-terminal segment of haemadin binds to the active site of thrombin, forming a parallel beta-strand with residues Ser214-Gly216 of the proteinase. This mode of binding is similar to that observed in another leech-derived inhibitor, hirudin. In contrast to hirudin, however, the markedly acidic C-terminal peptide of haemadin does not bind the fibrinogen-recognition exosite, but interacts with the heparin-binding exosite of thrombin. Thus, haemadin binds to thrombin according to a novel mechanism, despite an overall structural similarity with hirudin. Haemadin inhibits both free and thrombomodulin-bound alpha-thrombin, but not intermediate activation forms such as meizothrombin. This specific anticoagulant ability of haemadin makes it an ideal candidate for an antithrombotic agent, as well as a starting point for the design of novel antithrombotics.
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