The molecular basis of thrombin allostery revealed by a 1.8 A structure of the "slow" form.
Research article published in Structure (London, England : 1993) (2003)
Abstract
Thrombin participates in its own positive and negative feedback loops, and its allosteric state helps determine the hemostatic balance. Here we present the 1.8 A crystallographic structure of S195A thrombin in two conformational states: active site occupied and active site free. The active site-occupied form shows how thrombin can accommodate substrates, such as protein C. The active site-free form is in a previously unobserved closed conformation of thrombin, which satisfies all the conditions of the so-called "slow" form. A mechanism of allostery is revealed, which relies on the concerted movement of the disulphide bond between Cys168 and 182 and aromatic residues Phe227, Trp215, and Trp60d. These residues constitute an allosteric switch, which is flipped directly through sodium binding, resulting in the fast form with an open active site.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Thrombin participates in its own positive and negative feedback loops, and its allosteric state helps determine the hemostatic balance. Here we present the 1.8 A crystallographic structure of S195A thrombin in two conformational states: active site occupied and active site free.
Por qué esto importa para la hirudoterapia
This study presented a 1.8 Å crystal structure of the S195A thrombin mutant in two conformational states—active site occupied and active site free—revealing a previously unobserved closed conformation satisfying conditions of the 'slow' form. The authors identified an allosteric switch involving the Cys168-Cys182 disulfide bond and aromatic residues Phe227, Trp215, and Trp60d that is flipped directly through sodium binding, resulting in the fast form with an open active site. The work advances understanding of thrombin allosteric regulation relevant to coagulation biology broadly. CAVEAT: No hirudin, leech-derived compounds, or hirudotherapy are mentioned anywhere in the abstract; the connection to ASH's domain is entirely indirect through thrombin structural biology, and no defensible leech link exists.
Citación
The molecular basis of thrombin allostery revealed by a 1.8 A structure of the "slow" form.
Huntington et al. · Structure (London, England : 1993), 2003
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Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: June 18, 2026