Allosteric activation of antithrombin is independent of charge neutralization or reversal in the heparin binding site.
Allosteric activation of antithrombin is independent of charge neutralization or reversal in the heparin binding site.
复制标题
抗凝血酶的变构激活与肝素结合位点的电荷中和或逆转无关。
DOI：
10.1016/j.febslet.2006.07.057
复制
发表时间：
2006
期刊：
影响因子：
3.5
通讯作者：
Huntington,JamesA
中科院分区：
文献类型：
--
作者：
Langdown,Jonathan;Carter,WendyJ;Baglin,TrevorP;Huntington,JamesA
We investigate the hypothesis that heparin activates antithrombin (AT) by relieving electrostatic strain within helix D. Mutation of residues K125 and R129 to either Ala or Glu 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.
