Allosteric activation of antithrombin is independent of charge neutralization or reversal in the heparin binding site

作者：Langdown Jonathan; Carter Wendy J; Baglin Trevor P; Huntington James A^*

来源：FEBS Letters, 2006, 580(19): 4709-4712.

DOI：10.1016/j.febslet.2006.07.057

• serpin
• protease
• allostery
• hemostasis
• thrombosis

We investigate the hypothesis that heparin activates antithrombin (AT) by relieving electrostatic strain within helix D. Mutation of residues K125 and 8129 to either Ala or Gin abrogated heparin binding, but did not activate AT towards inhibition of factors IXa or Xa. However, substitution of residues C-terminal to helix D (R132 and K133) to Ala had minimal effect on heparin affinity but resulted in appreciable activation. We conclude that charge neutralization or reversal in the heparin binding site does not drive the activating conformational change of AT, and that the role of helix D elongation is to stabilize the activated state.

• 出版日期2006-8-21
• 单位河北医科大学