Crystal structure of a biosynthetic sulfo-hirudin complexed to thrombin
Crystal structure of a biosynthetic sulfo-hirudin complexed to thrombin
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DOI：
10.1021/ja0735002
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发表时间：
2007-09-05
影响因子：
15
通讯作者：
Schultz, Peter G.
中科院分区：
文献类型：
--
作者：
Liu, Chang C.;Brustad, Eric;Schultz, Peter G.
水蛭源性抗凝剂水蛭素在酪氨酸 63 上进行翻译后硫酸化，导致其对凝血酶的亲和力增加 > 10 倍。我们报告了与凝血酶复合的生物合成磺基水蛭素的结构，分辨率为 1.84 埃，并表明硫酸化是盐桥和扩展氢键网络的原因，这两者共同解释了磺基水蛭素与凝血酶亲和力的增加。我们还确定了凝血酶两个亚基之间界面上的二价阳离子结合位点，该位点可以调节凝血酶的生理活性。
The leech-derived anticoagulant hirudin is post-translationally sulfated on tyrosine 63, resulting in a > 10-fold increase in its affinity for thrombin. We report the structure of a biosynthetic sulfo-hirudin complexed to thrombin solved to 1.84 angstrom resolution and show that sulfation is responsible for a salt bridge and an extended hydrogen-bond network that taken together account for the increased affinity of sulfo-hirudin for thrombin. We also identify a divalent cation binding site at the interface between the two subunits of athrombin that may modulate the physiological activity of thrombin.