Structural Studies Of Two Snake Venom C-type Lectins

1. Structural study on agkisacucetin, an anti-GP I b snaclec (snake C-type lectin) from Agkistrodon acutusPlatelet adhesion to a damaged blood vessel is the initial trigger for arterial hemostasis and thrombosis. Agkisacucetin is a snake C-type lectin isolated from the venom of Agkistrodon acutus(A. acutus). It inhibits platelet by binding to GP I b and blocking the access of VWF to GP Ⅰ b. We have determined the crystal structure of agkisacucetin and refined to1.91A. The structure of agkisacucetin shares a very similar (αβ) structure with another GP I b-binding protein flavocetin-A, but without the C-termini cysteine in the β-subunit, agkisacucetin does not form an (αβ)4tetramer or cluster GP I bs like flavocetin-A. An unpaired cysteine in the a-subunit was found being modified to a cysteinesulfonic acid.2. Structural study on2K001, an anti-angiogenesis snaclec (snake C-type lectin) from Agkistrodon acutusMore than90%of all cancers present as solid tumors which depend on a functioning vascular network to supply oxygen and nutrients. Angiogenesis is the formation of new blood vessels from the pre-existing ones and it is a necessary process in tumors growing. The therapeutic strategy of interfering with angiogenesis holds great promise for cancer therapy.2K001, a snake C-type lectin isolated from the venom of Agkistrodon acutus (A. acutus) by Zhaoke Pharmaceutical (hefei) Co., Ltd., is a potencial anti-angiogenic agent. We have determined the crystal structure of2K001and refined to2.05A.2K001shares a high degree of sequence and structural similarity with EMS16, an integrin α2β1-binding protein. Integrin α2-I-domain was then cloned, expressed and was found to actually interact with2K001. Since integrin β2β1plays key role in angiogenesis,2K001may inhibit angiogenesis by interacting with integrin α2β1. This result provides a clue for the mechanism research on2K001.