Crystal Structure of the Disintegrin Heterodimer from Saw-Scaled Viper (Echis carinatus) at 1.9 Å Resolution

Disintegrins constitute a family of potent polypeptide inhibitors of integrins. Integrins are transmembrane heterodimeric molecules involved in cell−cell and cell−extracellular matrix interactions. They are involved in many diseases such as cancer and thrombosis. Thus, disintegrins have a great potential as anticancer and antithrombotic agents. A novel heterodimeric disintegrin was isolated from the venom of saw-scaled viper (Echis carinatus) and was crystallized. The crystals diffracted to 1.9 A resolution and belonged to space group P43212. The data indicated the presence of a pseudosymmetry. The structure was solved by applying origin shifts to the disintegrin homodimer schistatin solved in space group I4122 with similar cell dimensions. The structure refined to the final Rcryst/Rfree factors of 0.213/0.253. The notable differences are observed between the loops, (Gln39−Asp48) containing the important Arg42-Gly43-Asp44, of the present heterodimer and schistatin. These differences are presumably due to ...