English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Cancer metastasis is an important criterion to evaluate tumor malignancy. Matrix metalloproteinases (MMPs) play a crucial role in cancer proliferation and migration by virtue of their proteolytic functions in angiogenesis and extracelluar matrix (ECM) degradation, making them potential targets of anti-metastaic therapeutics. Recently we showed with both in vivo and in vitro experiments that metallofullerenol Gd@C82(OH)22 can effectively inhibit MMP-2 and MMP-9 with high antitumoral efficacy. Furthermore, our in silico study revealed that Gd@C82(OH)22 could indirectly inhibit the proteolysis of MMP-9 via allosteric modulation exclusively at the ligand specificity S1' loop. Here, we expand our study toward another gelatinase, MMP-2, using molecular dynamics simulations. Despite the high structural similarity with 64.3% sequence identity, their responses to Gd@C82(OH)22 were quite different. Toward MMP-2, Gd@C82(OH)22 could block either the Zn(2+)-catalylitic site directly or the S1' loop indirectly. Surface electrostatics uniquely determines the initial adsorption of Gd@C82(OH)22 on MMP-2, and then its further location of the most favorable binding site(s). These findings not only illustrated how the inhibitory mechanism of Gd@C82(OH)22 is distinguished between the two gelatinase MMPs with atomic details, but also shed light on the de novo design of anti-metastatic nanotherapeutics with enhanced target specificity.

Dual Inhibitory Pathways of Metallofullerenol Gd@C82(OH)22 on Matrix Metalloproteinase-2: Molecular insight into drug-like nanomedicine