Work

Crystal Structure of a Biosynthetic Sulfo-hirudin Complexed to Thrombin

Year: 2007

Type: article

Abstract: 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 α-thrombin that may modulate the physiological activity of thrombin.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja0735002

Authors: Chang C. Liu, Eric Brustad, Wenshe Liu, Peter G. Schultz

Institution: Scripps Research Institute

Language: English

Topic: Leech Biology and Applications

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Awards: G5183648865, G792181733