Structural Insight into Integrin Recognition and Anticancer Activity of Echistatin.

ABSTRACT: Echistatin (Ech) is a short disintegrin with a long ⁴²NPHKGPAT C-terminal tail. We determined the 3-D structure of Ech by X-ray crystallography. Superimposition of the structures of chains A and B showed conformational differences in their RGD loops and C-termini. The chain A structure is consistent with our NMR analysis that the GPAT residues of the C-terminus cannot be observed due to high flexibility. The hydrogen bond patterns of the RGD loop and between the RGD loop and C-terminus in Ech were the same as those of the corresponding residues in medium disintegrins. The mutant with C-terminal HKGPAT truncation caused 6.4-, 7.0-, 11.7-, and 18.6-fold decreases in inhibiting integrins αvβ3, αIIbβ3, αvβ5, and α5β1. Mutagenesis of the C-terminus showed that the H44A mutant caused

SUBMITTER: Chen YC 

PROVIDER: S-EPMC7695343 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature