Protease Inhibitors and Their Applications: An Overview

Marathe, Kiran; Patil, Ravindra H.; Vishwakarma, Kishor Sukhlal; Chaudhari, Ambalal; Maheshwari, Vijay L.

doi:10.1016/b978-0-444-64185-4.00006-x

Cited by 14 publications

(12 citation statements)

References 189 publications

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“…The inhibitors belonging to I01, I13 and I16 families show Laskowski or standard mechanism of binding 17 . However, members of Serpin (I04) family bind to the proteases irreversibly and bring about conformational changes in the enzyme 18,19 , therefore, all possible docked structures were considered for the Serpin whereas, for rest of the inhibitors protein-protein binding models that showed binding at the enzyme active sites were selected. Based on the cluster size and binding energies, it was seen that I16 (SSI_01) inhibitor showed strong binding with protease of Nocardiopsis sp.…”

Section: In-silico Studiesmentioning

confidence: 99%

Diversity and plasticity of simultaneously expressing extracellular protease inhibitors from four marine Streptomyces spp. isolated from West coast of India

Shintre

Deshpande

Patwardhan

et al. 2022

Preprint

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Streptomyces have long been studied for their defense metabolites and Protease Inhibitors (PIs) they secrete for mediating biotic interactions. Current study focuses on diversity of extracellular PIs obtained from four marine Streptomyces species isolated from intertidal regions of West Coast of India. Streptomyces PIs showed strong inhibition of subtilisin followed by trypsin and chymotrypsin. Using shotgun proteomics approach, we identified 15 Streptomyces PIs belonging to 4 PI families namely Streptomyces subtilisin inhibitor (SSI), Potato peptidase inhibitor, Ovomucoid and Serpin. This is a first report of identification of Ovomucoid and Potato peptidase inhibitor families from Streptomyces. Amongst the 15 PIs, 12 were SSIs with 20-75% sequence similarity and variations in the conserved 73rd aa residue. Moreover, 10 SSI isoforms were co-expressed in a single species S. longispororuber. In-silico and in-vitro assays with proteases from microbial, bovine and insect sources suggested that the Streptomyces PIs had a broad-spectrum inhibitory activity. In co-culture of Streptomyces with other protease producing bacteria, cellular secretions differentially affected growth, sporulation and/or pigment production. Present study elucidates the diversity and plasticity of extracellular PIs from marine Streptomyces spp. Further, their role in chemical ecology of the bacterial communities as well as their potential applications in therapeutics are discussed.

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Section: In-silico Studiesmentioning

confidence: 99%

Diversity and plasticity of simultaneously expressing extracellular protease inhibitors from four marine Streptomyces spp. isolated from West coast of India

Shintre

Deshpande

Patwardhan

et al. 2022

Preprint

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show abstract

“…In addition to this, Elkington argued that such pathogens could also purposefully secrete microbial proteases to skew the immune response towards tissue damage to promote invasion (Table 2). There are a number of proteases, which are classified according to their catalytic mechanism-based on the configuration of the active site [66], and the reader may peruse several databases that provide information on proteases, such as MEROPS (https://www. ebi.ac.uk/merops, accessed on 28 June 2021), Degradome (http://degradome.uniovi.es, accessed on 1 July 2021) and Proteolysis map (https://web.archive.org/web/2017042007 1011/http://sonny.burnham.org/proteases, accessed on 1 July 2021) [67][68][69].…”

Section: Possible Role Of Cryptococcal Proteases In Promoting Brain Invasion In the Context Of Co-infection With Sars-cov-2mentioning

confidence: 99%

“…Like other enzymes in living systems, the action of proteases is also tightly controlled by inhibitors, which can arrest their catalytic activity. Animal (vertebrate) protease inhibitors are localised in tissues as secretory proteins that block the activity of endogenous and exogenous proteases to prevent unwanted proteolysis [66]. Commercial sources of serine-based protease inhibitors, some of which are biologically extracted and purified, showing specificity towards mammalian serine proteases, may be useful in this regard.…”

Section: Promotes Spike Protein Cleavage and Activation For Membrane Fusion And Viral Uptakementioning

confidence: 99%

The Possible Role of Microbial Proteases in Facilitating SARS-CoV-2 Brain Invasion

Mjokane

Folorunso

Ogundeji

et al. 2021

Biology

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SARS-CoV-2 has been shown to display proclivity towards organs bearing angiotensin-converting enzyme (ACE2) expression cells. Of interest herein is the ability of the virus to exhibit neurotropism. However, there is limited information on how this virus invades the brain. With this contribution, we explore how, in the context of a microbial co-infection using a cryptococcal co-infection as a model, SARS-CoV-2 could reach the brain. We theorise that the secretion of proteases by disseminated fungal cells might also activate the S2 domain of the viral spike glycoprotein for membrane fusion with brain endothelial cells leading to endocytosis. Understanding this potential invasion mechanism could lead to better SARS-CoV-2 intervention measures, which may also be applicable in instances of co-infection, especially with protease-secreting pathogens.

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“…LSPILT can be used as a prototype (taking into account the participation of serpins in a large number of biological events and in human health) for analyzes concerning biotechnological applicabilities, as previously pointed for other serpin family-members (Gaci et al, 2013). Regarding cell biology experimental studies, the recombinant LSPILT can be used as a prototype in protocols aiming to unveil how cells proliferate, migrate, undergo to apoptosis and control cellular protein half-life (Marathe et al, 2019). Regarding the control of agricultural infestations, LSPILT can be investigated as a potential input, since serpins have been shown as molecules able to inhibit digestive enzymes present in the gastrointestinal tract of insect, inducing an insecticide effect (Clemente et al, 2019).…”

Section: Brown Spider Venom Moleculesmentioning

confidence: 99%

Prospective Use of Brown Spider Venom Toxins as Therapeutic and Biotechnological Inputs

Gremski

Matsubara

Polli

et al. 2021

Front. Mol. Biosci.

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Brown spider (genus Loxosceles) venoms are mainly composed of protein toxins used for predation and defense. Bites of these spiders most commonly produce a local dermonecrotic lesion with gravitational spread, edema and hemorrhage, which together are defined as cutaneous loxoscelism. Systemic loxoscelism, such as hematological abnormalities and renal injury, are less frequent but more lethal. Some Loxosceles venom toxins have already been isolated and extensively studied, such as phospholipases D (PLDs), which have been recombinantly expressed and were proven to reproduce toxic activities associated to the whole venom. PLDs have a notable potential to be engineered and converted in non-toxic antigens to produce a new generation of antivenoms or vaccines. PLDs also can serve as tools to discover inhibitors to be used as therapeutic agents. Other Loxosceles toxins have been identified and functionally characterized, such as hyaluronidases, allergen factor, serpin, TCTP and knottins (ICK peptides). All these toxins were produced as recombinant molecules and are biologically active molecules that can be used as tools for the potential development of chemical candidates to tackle many medical and biological threats, acting, for instance, as antitumoral, insecticides, analgesic, antigens for allergy tests and biochemical reagents for cell studies. In addition, these recombinant toxins may be useful to develop a rational therapy for loxoscelism. This review summarizes the main candidates for the development of drugs and biotechnological inputs that have been described in Brown spider venoms.

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Protease Inhibitors and Their Applications: An Overview

Cited by 14 publications

References 189 publications

Diversity and plasticity of simultaneously expressing extracellular protease inhibitors from four marine Streptomyces spp. isolated from West coast of India

Diversity and plasticity of simultaneously expressing extracellular protease inhibitors from four marine Streptomyces spp. isolated from West coast of India

The Possible Role of Microbial Proteases in Facilitating SARS-CoV-2 Brain Invasion

Prospective Use of Brown Spider Venom Toxins as Therapeutic and Biotechnological Inputs

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