Protease propeptide structures, mechanisms of activation, and functions

Boon, Lise; Ugarte-Berzal, Estefanía; Vandooren, Jennifer; Opdenakker, Ghislain

doi:10.1080/10409238.2020.1742090

Cited by 57 publications

(41 citation statements)

References 521 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to controlling protease activity, prodomains have been shown to play an important role in folding and trafficking. 35 The mechanism of interaction made by the prodomain, particularly in orientation of the C-terminal "stalk" region along the "active-site" groove to occlude the substratebinding cleft, is similar in molecular design to comparable proteases (Figure 2). The orientation of the prodomain conventionally serves to ablate catalytic activity by binding to the active site in the reverse direction to that of native substrates; reducing the availability of the proteases to bind and cleave substrate.…”

Section: Interaction Between Pro and Central Domainsmentioning

confidence: 99%

“…The orientation of the prodomain conventionally serves to ablate catalytic activity by binding to the active site in the reverse direction to that of native substrates; reducing the availability of the proteases to bind and cleave substrate. 35,42 Activation of zymogens by removal of the prodomain leads to activation of the catalytic domain. Notably, the PfSERA5 prodomain is orientated through the active-site cleft in this same reverse direction.…”

Section: Interaction Between Pro and Central Domainsmentioning

confidence: 99%

“…34 Prodomains are known to act with a myriad of functions to ensure correct folding, to prevent premature enzymatic activation by occupation of the active site groove, and in chaperoning. 35 In this study we present a higher resolution crystal structure of the central papain-like domain (Asp563-Asn827: PfSERA5E). More importantly, we demonstrate that the N-terminal region of P50 indeed does comprises a papain-like prodomain, resembling cathepsin prodomains in overall tertiary structure, and with similar interactions to the associated central papain-like domain.…”

Section: Introductionmentioning

confidence: 99%

“…This region, which is thought to remain bound to the papain‐like domain, has previously been shown to have an inhibitory effect on merozoite egress 34 . Prodomains are known to act with a myriad of functions to ensure correct folding, to prevent premature enzymatic activation by occupation of the active site groove, and in chaperoning 35 …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Structure of the Plasmodium falciparum PfSERA5 pseudo‐zymogen

Smith

Clarke

et al. 2020

Protein Science

View full text Add to dashboard Cite

PfSERA5, a significantly abundant protein present within the parasitophorous vacuole (PV) and essential for normal growth during the blood-stage life cycle of the malaria parasite Plasmodium falciparum, displays structural similarity to many other cysteine proteases. However, PfSERA5 does not exhibit any detectable protease activity and therefore the role of the PfSERA5 papain-like domain (PfSERA5E), thought to remain bound to its cognate prodomain, remains unknown. In this study, we present a revised structure of the central PfSERA5E domain at a resolution of 1.2 Å, and the first structure of the "zymogen" of this papain-like domain including its cognate prodomain (PfSERA5PE) to 2.2 Å resolution. PfSERA5PE is somewhat structurally similar to that of other known proenzymes, retaining the conserved overall folding and orientation of the prodomain through, and occluding, the archetypal papain-like catalytic triad "active-site" cleft, in the same reverse direction as conventional prodomains. Our findings are congruent with previously identified structures of PfSERA5E and of similar "zymogens" and provide a foundation for further investigation into the function of PfSERA5.

show abstract

Section: Interaction Between Pro and Central Domainsmentioning

confidence: 99%

Section: Interaction Between Pro and Central Domainsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Structure of the Plasmodium falciparum PfSERA5 pseudo‐zymogen

Smith

Clarke

et al. 2020

Protein Science

View full text Add to dashboard Cite

show abstract

“…Proteases, peptidases, proteinases or proteolytic enzymes are hydrolases that catalyze the breakdown of peptide bonds in proteins (Gurumallesh et al, 2019). These biocatalysts play physiological functions essential for the maintenance of the life of living beings, such as cell signaling, inflammation, apoptosis, blood coagulation and hormone processing (Bond, 2019;Boon et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Lentinus Villosus Klotzsch (1833) Am 169: A Natural and Renewable Source of Alkaline Protease / Lentinus Villosus Klotzsch (1833) Am 169: Uma Fonte Natural E Renovável De Protease Alcalina

Braga¹,

Brito

Souza

et al. 2020

BJD

View full text Add to dashboard Cite

Mushrooms have stood out as sources of proteases with industrial applicability. The objective of this work was to evaluate the parameters that influence the synthesis of proteases by Lentinus villosus Klotzsch (1833) AM 169 and to characterize these enzymes. The matrix culture, prepared on potato dextrose agar supplemented with yeast extract, was maintained for 8 days at 25 ° C. Submerged fermentation was carried out in GYPG (glucose, yeast extract, peptone and gelatin). Azocasein solution (1%, w/v) was used as an enzyme substrate. The best conditions for protease production were: initial pH of the culture medium (6), fermentation time (12 days), age of the inoculum (6 days) and size of the inoculum (10%). The proteases were active at pH 8, at 60 ° C, stable at pH (5 to 9) and temperature (30 °C to 60 °C). These enzymes were classified as cysteine proteases, stimulated by Fe 2+ and Mn 2+. Lentinus villosus synthesizes proteases with potential for application in the detergent, textile, leather processing and bioremediation processes.

show abstract

Versatility of subtilisin: A review on structure, characteristics, and applications

Azrin

Ali

Rahman

et al. 2022

Biotech and App Biochem

View full text Add to dashboard Cite

Due to its thermostability and high pH compatibility, subtilisin is most known for its role as an additive for detergents in which it is categorized as a serine protease according to MEROPS database. Subtilisin is typically isolated from various bacterial species of the Bacillus genus such as Bacillus subtilis, B. amyloliquefaciens, B. licheniformis, and various other organisms. It is composed of 268-275 amino acid residues and is initially secreted in the precursor form, preprosubtilisin, which is composed of 29-residues signal peptide, 77-residues propeptide, and 275-residues active subtilisin. Subtilisin is known for the presence of high and low affinity calcium binding sites in its structure. Native subtilisin has general properties of thermostability, tolerance to neutral to high pH, broad specificity, and calcium-dependent stability, which contribute to the versatility of subtilisin applicability. Through protein engineering and immobilization technologies, many variants of subtilisin have been generated, which increase the applicability of subtilisin in various industries including detergent, food processing and packaging, synthesis of inhibitory peptides, therapeutic, and waste management applications.

show abstract

Protease propeptide structures, mechanisms of activation, and functions

Cited by 57 publications

References 521 publications

Structure of the Plasmodium falciparum PfSERA5 pseudo‐zymogen

Structure of the Plasmodium falciparum PfSERA5 pseudo‐zymogen

Lentinus Villosus Klotzsch (1833) Am 169: A Natural and Renewable Source of Alkaline Protease / Lentinus Villosus Klotzsch (1833) Am 169: Uma Fonte Natural E Renovável De Protease Alcalina

Versatility of subtilisin: A review on structure, characteristics, and applications

Contact Info

Product

Resources

About