The Na+ binding site of thrombin.
Research article published in The Journal of biological chemistry (1995)
Abstract
Thrombin is an allosteric serine protease existing in two forms, slow and fast, targeted toward anticoagulant and procoagulant activities. The slow --> fast transition is induced by Na+ binding to a site contained within a cylindrical cavity formed by three antiparallel beta-strands of the B-chain (Met180-Tyr184a, Lys224-Tyr228, and Val213-Gly219) diagonally crossed by the Glu188-Glu192 strand. The site is shaped further by the loop connecting the last two beta-strands and is located more than 15 A away from the catalytic triad. The cavity traverses through thrombin from the active site to the opposite surface and contains Asp189 of the primary specificity site near its midpoint. The bound Na+ is coordinated octahedrally by the carbonyl oxygen atoms of Tyr184a, Arg221a, and Lys224, and by three highly conserved water molecules in the D-Phe-Pro-Arg chloromethylketone thrombin. The sequence in the Na+ binding loop is highly conserved in thrombin from 11 different species and is homologous to that found in other serine proteases involved in blood coagulation. Mutation of two Asp residues flanking Arg221a (D221A/D222K) almost abolishes the allosteric properties of thrombin and shows that the Na+ binding loop is also involved in direct recognition of protein C and antithrombin.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Thrombin is an allosteric serine protease existing in two forms, slow and fast, targeted toward anticoagulant and procoagulant activities. The slow --> fast transition is induced by Na+ binding to a site contained within a cylindrical cavity formed by three antiparallel beta-strands of the B-chain...
Por qué esto importa para la hirudoterapia
El resumen caracteriza la base estructural del sitio de unión de Na+ de la trombina, identificando la cavidad de la cadena beta, los residuos y las moléculas de agua que participan en la coordinación octaédrica de Na+, y reporta que las mutaciones D221A/D222K cercanas al bucle de unión de Na+ casi abolieren las propiedades alostéricas de la trombina y afectan el reconocimiento de la proteína C y la antitrombina. Este trabajo versa sobre la alostericidad de la trombina y la especificidad de las proteasas de la coagulación sanguínea. Sin embargo, el resumen no menciona sanguijuelas, hirudina, hirudoterapia ni ningún compuesto derivado de sanguijuela, por lo que no aporta evidencia directa relevante para el ámbito de la ASH. Su relevancia se limita a la biología estructural general de la trombina, no a terapéuticas basadas en sanguijuelas o derivadas de ellas.
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Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: 18 de junio de 2026