Distinct structural basis and catalytic classification of matrix metalloproteinases and their endogenous tissue inhibitors with glycosylation issue in cellular and tissue regulation

Abstract

Matrix metalloproteinase (MMP) enzymes cleave proteins on the extracellular matrix (ECM) region. MMPs are categorized as Zn2+-binding endo-proteinases. MMPs are stringently regulated in cancers, inflammatory cells and tissues. There are 29 types of MMPs as initially expressed in inactive zymogens (proMMPs) and activated by proteolysis in vertebrates including human. MMPs consist of three highly conserved parts of pro-MMP in precursor, catalytic and hemopexin domains. The MMPs are composed of systemic complexes with their endogenously expressed inhibitors of the tissue inhibitors of metalloproteinases (TIMPs). Therefore, TIMPs intrinsically control such activated MMPs, indicating the existence of self-modulation capacity. N-linked glycosylation (N-glycosylation) saves biological information than known phosphorylation, ubiquitination and acetylation. The MMPs are roughly present as membrane-merged and secreted glycoproteins. MMPs N-glycans regulate cellular behaviors, immune tolerance, and developing angiogenesis. Aberrant N-glycosylation of MMPs may cause the pathogenic properties. N-glycosylation shapes phenotypes of MMPs-producing cells during early MMPs involved in human. Additionally, issues of MMPs and TIMPs glycosylation have been described to view the importance of the glycans in their interaction with owns and other targets. Most of MMPs and 4 TIMPs are not well studied for their glycosylation and its functional roles.