enzyme

Metallo-matrixprotein 9 (MMP9)

MMPs (matrix metalloproteinases) are zinc-dependent endopeptidases with more than 20 different members (Klein and Bischoff, 2011). MMPs can be divided into six main groups, such as gelatinases, collagenases, matrilysins, stromelysins, membrane-type MMPs, and others (Nagase et al., 2006). In particular, MMP-9, a member of the gelatinase family, is one of the most complex action-performing MMPs, as it plays a key role in cancer cell invasion, tumor metastasis, and triggering the “angiogenic switch” (Bronisz and Kurkowska-Jastrzębska, 2016). During tissue remodeling, it degrades gelatin and types IV, V, XI, and XVI collagen, which are essential for tumor invasion and metastasis (Liu et al., 2015). Additionally, MMP-9 also acts as a functional component of angiogenesis switch during multistage carcinogenesis, where MMP-9 triggers the release of a vascular epidermal growth factor, which accelerates tumor growth (Engsig et al., 2000). MMP-9 is commonly found in the hippocampus, cerebellum, and cerebral cortex. It is secreted mainly from the endothelial cells, leukocytes, fibroblasts, neutrophils, and macrophages as zymogens or in an inactive form (Bronisz and Kurkowska-Jastrzębska, 2016). Human MMP-9 proteins generally consist of three domains: the N-terminal propeptide domain, the catalytic domain, and the C-terminal, the hemopexin-like domain. The catalytic domain of human MMP-9 which is without the fibronectin repeats has the same structure as other MMPs: a five-stranded beta-sheet and three alpha-helices. It is composed of the active-site zinc ion, coordinated by three histidine residues (401, 405, and 411) and the essential glutamic acid residue (402). The catalytic zinc ion is essential for proteolytic activity (Bode et al., 1999). The hemopexin-like domain of MMP-9 interacts with substrates like gelatin and collagen. This domain is crucial for substrate recognition (Roderfeld et al., 2007). Some natural tissue inhibitors of MMPs (TIMPs), such as TIMP-1, can bind to the hemopexin-like domain of pro-MMP-9 to form a tight complex that prevents MMP-9 from being activated (Nagase et al., 2006; Roderfeld et al., 2007).

Ref:
AUTHOR=Mathpal Shalini, Sharma Priyanka, Joshi Tushar, Pande Veena, Mahmud Shafi, Jeong Mi-Kyung, Obaidullah Ahmad J., Chandra Subhash, Kim Bonglee TITLE=Identification of Zinc-Binding Inhibitors of Matrix Metalloproteinase-9 to Prevent Cancer Through Deep Learning and Molecular Dynamics Simulation Approach JOURNAL=Frontiers in Molecular Biosciences VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/articles/10.3389/fmolb.2022.857430 DOI=10.3389/fmolb.2022.857430 ISSN=2296-889X

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Added on Mar 11, 2023 by Barbara Van De Keer
Edited on Jul 23, 2023 by Barbara Van De Keer

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