Serine protease inhibitors containing a Kunitz domain: their role in modulation of host inflammatory responses and parasite survival

Magalhães, Mariana T.Q. de; Mambelli, Fábio S.; Santos, Bruno P.O.; Morais, Suellen B.; Oliveira, Sérgio C.

doi:10.1016/j.micinf.2018.01.003

Cited by 20 publications

(14 citation statements)

References 34 publications

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“…9. Purified recombinant serpin 1270 inhibited Bacillus subtilisin belonging to the S8 family, a subfamily of the MEROPS peptidase database (4).…”

Section: Resultsmentioning

confidence: 99%

“…Serine proteases are the major target of serpins, but some serpins, such as cysteine proteases (e.g., viral serpin crmA with caspase-1, SCCA-1, and MENT), inhibit proteases other than serine proteases (2). Not all serpins are inhibitory proteins; some noninhibitory serpins play a major role in physiological pathways such as blood coagulation, fibrinolysis, hormone binding, intracellular signaling, and programmed cell death and can be used as a therapeutic agent against gram-positive and gram-negative bacteria (3,4,5). Maspins, a class of mammary serpins, can be used as a potential marker for the screening of esophageal cancers (6).…”

Section: Introductionmentioning

confidence: 99%

“…The primary function of serpins is to neutralize the effect of serine proteases (12). Kang et al (4), for the first time, reported the presence of two serpin-like genes in the C. thermocellum cellulosome, which showed high sequence identity with the serpin from Thermobifida fusca , which also contained a dockerin module like those of other dockerins present in the C. thermocellum cellulosome.…”

Section: Introductionmentioning

confidence: 99%

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Serpins: Purification and characterization of potent protease inhibitors fromClostridium thermocellum

Mushtaq

Asad

Naqvi

et al. 2020

Preprint

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Clostridiumthermocellum produces an extracellular cellulosome (a multiprotein complex produced by firmicutes bacteria), which, owing to its extracellular location, is open to protease attack. Serine protease inhibitors (serpins) protect bacteria against protease attack. However, their structure and function are poorly characterized. This study identified and amplified the serpin 1270 gene from the C. thermocellum genome. Purified serpins were cloned into the pTXB1 vector using the one-step sequence and ligation-independent cloning reaction and transformed into Escherichia coli BL21 DE3 cells. Enzyme overexpression and purification and enzyme inhibitory assays were performed. The results showed that serpin 1270 has 89% inhibition against Bacillus subtilisin and 64% inhibition against trypsin, chymotrypsin, and papain.

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“…9. Purified recombinant serpin 1270 inhibited Bacillus subtilisin belonging to the S8 family, a subfamily of the MEROPS peptidase database (4).…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Serpins: Purification and characterization of potent protease inhibitors fromClostridium thermocellum

Mushtaq

Asad

Naqvi

et al. 2020

Preprint

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“…It has been proven that the presence of either Lysine or Arginine at the P1 position obstructs any protease from cleaving adjacently to those residues in the protein substrate, while the Asn13, Tyr17 and Tyr18 stabilize the canonical loop in the reactive site [ 47 ]. These features are central to the biological activity of the protein and permit the orientation of its functional moieties [ 48 ]. At the outset of interaction, the serpin binds to proteases through a non-covalent Michaelis-like complex, which is formed through interactions with residues flanking the scissile bond (P1-P1′) within the RCL, forming a transient covalent ester linkage [ 49 , 50 ].…”

Section: Protease Inhibitors and Schistosomiasismentioning

confidence: 99%

Proteins as Targets in Anti-Schistosomal Drug Discovery and Vaccine Development

2021

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Proteins hardly function in isolation; they form complexes with other proteins or molecules to mediate cell signaling and control cellular processes in various organisms. Protein interactions control mechanisms that lead to normal and/or disease states. The use of competitive small molecule inhibitors to disrupt disease-relevant protein–protein interactions (PPIs) holds great promise for the development of new drugs. Schistosome invasion of the human host involves a variety of cross-species protein interactions. The pathogen expresses specific proteins that not only facilitate the breach of physical and biochemical barriers present in skin, but also evade the immune system and digestion of human hemoglobin, allowing for survival in the host for years. However, only a small number of specific protein interactions between the host and parasite have been functionally characterized; thus, in-depth understanding of the molecular mechanisms of these interactions is a key component in the development of new treatment methods. Efforts are now focused on developing a schistosomiasis vaccine, as a proposed better strategy used either alone or in combination with Praziquantel to control and eliminate this disease. This review will highlight protein interactions in schistosomes that can be targeted by specific PPI inhibitors for the design of an alternative treatment to Praziquantel.

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“…The team of Oliveiro reminds us that sometimes the foe can become a friend, at least in bits and pieces. They make a good case for the use of serine protease inhibitors containing a Kunitz domain normally used by helminth parasites to dampen the host immune system, but which could come in very handy when the latter goes over the top [22]. In turn, Olds et al plead for the revival of an "ancient universal stress molecule" -abscisic acid (ABA).…”

Section: Times Of Treatmentsmentioning

confidence: 99%

Microbes and Infection turns 20

Häfner

Ojcius

2018

Microbes and Infection

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The journal Microbes and Infection is celebrating its vigintennial anniversary and has reunited for this occasion two dozen reviews illustrating achievements of the past as well as future challenges in the field of infectious diseases. From top-notch vaccine development strategies, to high-throughput powered analysis of complex host-pathogen interactions, to innovative therapeutic designs, this issue covers the entire spectrum of pathogens and areas of their confrontation with the host.

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Serine protease inhibitors containing a Kunitz domain: their role in modulation of host inflammatory responses and parasite survival

Cited by 20 publications

References 34 publications

Serpins: Purification and characterization of potent protease inhibitors fromClostridium thermocellum

Serpins: Purification and characterization of potent protease inhibitors fromClostridium thermocellum

Proteins as Targets in Anti-Schistosomal Drug Discovery and Vaccine Development

Microbes and Infection turns 20

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