Crystal Structure of a Biosynthetic Sulfo-hirudin Complexed to Thrombin

详细信息    查看全文

• 作者：Chang C. Liu ; Eric Brustad ; Wenshe Liu ; Peter G. Schultz
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：September 5, 2007
• 年：2007
• 卷：129
• 期：35
• 页码：10648 - 10649
• 全文大小：91K
• 年卷期：v.129,no.35(September 5, 2007)
• ISSN：1520-5126

文摘

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 Å 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 -thrombin that may modulate the physiological activity of thrombin.