ArticleMicrobial cell factories2017
Direct expression of active human tissue inhibitors of metalloproteinases by periplasmic secretion in Escherichia coli.
Article in Microbial cell factories, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- Monoclonal antibodies inhibiting MMP-9 activity alleviate peripheral neuropathy in diabetic mice.Science translational medicine · 2026Article
- Achieving protease substrate-specific inhibition by mAb dual functional selections.Protein science : a publication of the Protein Society · 2026Article
- Generation of Protease Inhibitory Antibodies by Functional In Vivo Selection.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Substrate derived sequences act as subsite-blocking motifs in protease inhibitory antibodies.Protein science : a publication of the Protein Society · 2023Article
- Strategies for enriching and characterizing proteins with inhibitory properties on the yeast surface.Protein engineering, design & selection : PEDS · 2023Article
- The CXCL12/CXCR7 signalling axis promotes proliferation and metastasis in cervical cancer.Medical oncology (Northwood, London, England) · 2021Article
- Generation of highly selective monoclonal antibodies inhibiting a recalcitrant protease using decoy designs.Biotechnology and bioengineering · 2020Article
- Protease Inhibition Mechanism of Camelid-like Synthetic Human Antibodies.Biochemistry · 2020Article
- Reducing proteolytic liability of a MMP-14 inhibitory antibody by site-saturation mutagenesis.Protein science : a publication of the Protein Society · 2019Article
- Degradation and Remodeling of Epitaxially Grown Collagen Fibrils.Cellular and molecular bioengineering · 2019Article
- The Preparation and Solution NMR Spectroscopy of Human Glycoproteins Is Accessible and Rewarding.Methods in enzymology · 2019Article
- Epitope-specific affinity maturation improved stability of potent protease inhibitory antibodies.Biotechnology and bioengineering · 2018Article
- Selectivity Conversion of Protease Inhibitory Antibodies.Antibody therapeutics · 2018Article
- Use of a novel camelid-inspired human antibody demonstrates the importance of MMP-14 to cancer stem cell function in the metastatic process.Oncotarget · 2018Article
- Contact guidance diversity in rotationally aligned collagen matrices.Acta biomaterialia · 2018Article
- Generation of Highly Selective MMP Antibody Inhibitors.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Functional Production of Catalytic Domains of Human MMPs in Escherichia coli Periplasm.Methods in molecular biology (Clifton, N.J.) · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAs regulators of multifunctional metalloproteinases including MMP, ADAM and ADAMTS families, tissue inhibitors of metalloproteinases (TIMPs) play a pivotal role in extracellular matrix remodeling, which is involved in a wide variety of physiological processes. Since abnormal metalloproteinase activities are related to numerous diseases such as arthritis, cancer, atherosclerosis, and neurological disorders, TIMPs and their engineered mutants hold therapeutic potential and thus have been extensively studied. Traditional productions of functional TIMPs and their N-terminal inhibitory domains (N-TIMPs) rely on costly and time-consuming insect and mammalian cell systems, or tedious and inefficient refolding from denatured inclusion bodies. The later process is also associated with heterogeneous products and batch-to-batch variation.
resultsIn this study, we developed a simple approach to directly produce high yields of active TIMPs in the periplasmic space of Escherichia coli without refolding. Facilitated by disulfide isomerase (DsbC) co-expression in protease-deficient strain BL21 (DE3), N-TIMP-1/-2 and TIMP-2 which contain multiple disulfide bonds were produced without unwanted truncations. 0.2-1.4 mg purified monomeric TIMPs were typically yielded per liter of culture media. Periplasmically produced TIMPs exhibited expected inhibition potencies towards MMP-1/2/7/14, and were functional in competitive ELISA to elucidate the binding epitopes of MMP specific antibodies. In addition, prepared N-TIMPs were fully active in a cellular context, i.e. regulating cancer cell morphology and migration in 2D and 3D bioassays.
conclusionPeriplasmic expression in E. coli is an excellent strategy to recombinantly produce active TIMPs and N-TIMPs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.