Unknown

Dataset Information

0

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 ?v?3, ?IIb?3, ?v?5, and ?5?1. Mutagenesis of the C-terminus showed that the H44A mutant caused 2.5- and 4.4-fold increases in inhibiting ?IIb?3 and ?5?1, and the K45A mutant caused a 2.6-fold decrease in inhibiting ?IIb?3. We found that Ech inhibited VEGF-induced HUVEC proliferation with an IC50 value of 103.2 nM and inhibited the migration of A375, U373MG, and Panc-1 tumor cells with IC50 values of 1.5, 5.7, and 154.5 nM. These findings suggest that Ech is a potential anticancer agent, and its C-terminal region can be optimized to improve its anticancer activity.

SUBMITTER: Chen YC 

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

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structural Insight into Integrin Recognition and Anticancer Activity of Echistatin.

Chen Yi-Chun YC   Chang Yao-Tsung YT   Chen Chiu-Yueh CY   Shiu Jia-Hau JH   Cheng Chun-Ho CH   Huang Chun-Hao CH   Chen Ju-Fei JF   Chuang Woei-Jer WJ  

Toxins 20201109 11


Echistatin (Ech) is a short disintegrin with a long <sup>42</sup>NPHKGPAT 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-terminu  ...[more]

Similar Datasets

| S-EPMC8241838 | biostudies-literature
| S-EPMC3799375 | biostudies-literature
| S-EPMC6044410 | biostudies-literature
| S-EPMC5584418 | biostudies-literature
| S-EPMC2740728 | biostudies-literature
| S-EPMC5374059 | biostudies-literature
| S-EPMC3494900 | biostudies-literature
| S-EPMC2651756 | biostudies-literature
| S-EPMC2865857 | biostudies-literature
| S-EPMC11343101 | biostudies-literature