Molecular interactions of tannic acid and matrix metalloproteinases 2 and 9

Ya-Tang Chiang; Yu-Bai Xiao; Shan-Hui Hsu; Shu-Wei Chang; Chia-Ching Chou

doi:10.1016/j.csbj.2023.04.011

Molecular interactions of tannic acid and matrix metalloproteinases 2 and 9

Comput Struct Biotechnol J. 2023 Apr 14:21:2792-2800. doi: 10.1016/j.csbj.2023.04.011. eCollection 2023.

Authors

Ya-Tang Chiang¹, Yu-Bai Xiao², Shan-Hui Hsu¹, Shu-Wei Chang^{2

3}, Chia-Ching Chou⁴

Affiliations

¹ Institute of Polymer Science and Engineering, National Taiwan University, Roosevelt Road No. 1, Section 4, 10617 Taipei, Taiwan.
² Department of Civil Engineering, College of Engineering, National Taiwan University, Roosevelt Road No. 1, Section 4, 10617 Taipei, Taiwan.
³ Department of Biomedical Engineering, College of Engineering, National Taiwan University, Roosevelt Road No. 1, Section 4, 10617 Taipei, Taiwan.
⁴ Institute of Applied Mechanics, College of Engineering, National Taiwan University, Roosevelt Road No. 1, Section 4, 10617 Taipei, Taiwan.

Abstract

Tannic acid (TA) has antibacterial, antioxidant, and anti-inflammatory properties and acts as an adhesive, hemostatic, and crosslinking agent in hydrogels. Matrix metalloproteinases (MMPs), a family of endopeptidase enzymes, play important roles in tissue remodeling and wound healing. TA has been reported to inhibit MMP-2/- 9 activities, thereby improving both tissue remodeling and wound healing. However, the mechanism of interaction of TA with MMP-2 and MMP-9 has not been fully elucidated. In this study, the full atomistic modeling approach was applied to explore the mechanisms and structures of TA binding with MMP-2 and MMP-9. Macromolecular models of the TA-MMP-2/- 9 complex were built by docking based on experimentally resolved MMP structures, and further equilibrium processes were examined by molecular dynamics (MD) simulations to investigate the binding mechanism and structural dynamics of the TA-MMP-2/- 9 complexes. The molecular interactions between TA and MMPs, including H-bond formation and hydrophobic and electrostatic interactions, were analyzed and decoupled to elucidate the dominant factors in TA-MMP binding. TA binds to MMPs mainly at two binding regions, residues 163-164 and 220-223 in MMP-2 and residues 179-190 and 228-248 in MMP-9. Two arms of TA participate in binding MMP-2 with 3.61 hydrogen bonds. On the other hand, TA binds MMP-9 with a distinct configuration involving four arms with 4.75 hydrogen bonds, resulting in a tighter binding conformation. Understanding the binding mechanism and structural dynamics of TA with these two MMPs provides crucial and fundamental knowledge regarding the inhibitory and stabilizing effects of TA on MMPs.

Keywords: Hydrogel; Matrix metalloproteinase 2; Matrix metalloproteinase 9; Molecular docking; Tannic acid.