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Information on EC 3.4.22.32 - Stem bromelain and Organism(s) Ananas comosus and UniProt Accession P14518
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3.4.22.32 Stem bromelainSpecify your search results
Word Map
- 3.4.22.32
- papain
- ficin
- comosus
- chymotrypsin
- ananas
- hydrolysates
- allergen
- proteinases
- ige
-
debridement
- neuraminidase
- alcalase
- cystatins
- virion
- hymenoptera
- flavourzyme
- medicine
- kininogens
-
prick
-
eschar
-
tender
-
haemagglutinins
- food industry
- actinidin
- ha2
- agriculture
- chymopapain
-
mucolytic
- pharmacology
- pancreatin
-
ige-binding
The taxonomic range for the selected organisms is: Ananas comosus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
broad specificity for cleavage of proteins, but strong preference for Z-Arg-Arg-/-NHMec amongst small molecule substrates
Synonyms
bromelain, stem bromelain, pineapple stem bromelain, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Bromelain
Bromelain, stem
-
-
-
-
Pineapple stem bromelain
Bromelain
-
-
-
-
Bromelain
-
-
Pineapple stem bromelain
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
37189-34-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
benzyl-Phe-Val-Arg-4-nitroanilide + H2O
benzyl-Phe-Val-Arg + 4-nitroaniline
-
-
-
?
benzyloxycarbonyl-Arg-Arg-4-nitroanilide + H2O
benzyloxycarbonyl-Arg-Arg + 4-nitroaniline
preferred substrate of stem bromelain
-
-
?
Benzoyl-Arg-Arg 4-nitrophenyl ester + H2O
Benzoyl-Arg-Arg + 4-nitrophenol
-
-
-
-
?
Benzoyl-citrulline 4-nitroanilide + H2O
Benzoyl-citrulline + 4-nitroaniline
-
-
-
-
?
Benzyloxycarbonyl-Arg-Arg 4-methylcoumarin 7-amide + H2O
Benzyloxycarbonyl-Arg-Arg + 7-amino-4-methylcoumarin
Benzyloxycarbonyl-Arg-Arg 4-nitrophenyl ester + H2O
Benzyloxycarbonyl-Arg-Arg + 4-nitrophenol
-
-
-
-
?
benzyloxycarbonyl-Arg-Arg-NH-4-methylcoumarin 7-amide + H2O
?
-
synthetic substrate
-
?
benzyloxycarbonyl-Arg-Arg-p-nitroanilide + H2O
benzyloxycarbonyl-Arg-Arg + p-nitroaniline
-
-
-
-
?
Benzyloxycarbonyl-citrulline 4-nitroanilide + H2O
Benzyloxycarbonyl-citrulline + 4-nitroaniline
-
-
-
-
?
Benzyloxycarbonyl-Gly 4-nitrophenyl ester + H2O
Benzyloxycarbonyl-Gly + 4-nitrophenol
-
-
-
-
?
Benzyloxycarbonyl-Gly-Phe-citrulline 4-methylcoumarin 7-amide + H2O
?
-
-
-
-
?
Benzyloxycarbonyl-Gly-Phe-Phe-citrulline 4-nitroanilide + H2O
?
-
best substrate
-
-
?
Benzyloxycarbonyl-L-Ala 4-nitrophenyl ester + H2O
Benzyloxycarbonyl-L-Ala + 4-nitrophenol
-
-
-
-
?
Benzyloxycarbonyl-L-Asn 4-nitrophenyl ester + H2O
Benzyloxycarbonyl-L-Asn + 4-nitrophenol
-
-
-
-
?
Benzyloxycarbonyl-L-Lys 4-nitrophenyl ester + H2O
Benzyloxycarbonyl-L-Lys + 4-nitrophenol
-
-
-
-
?
benzyloxycarbonyl-L-Tyr 4-nitrophenyl ester + H2O
benzyloxycarbonyl-L-Tyr + 4-nitrophenol
-
-
-
-
?
Benzyloxycarbonyl-Phe-Arg 4-methylcoumarin 7-amide + H2O
Benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
benzyloxycarbonyl-Phe-Arg-NH-4-methylcoumarin 7-amide + H2O
?
-
synthetic substrate
-
?
benzyloxycarbonyl-Phe-Val-Arg-NH-4-methylcoumarin 7-amide + H2O
?
-
synthetic substrate
-
?
Bz-Phe-Val-Arg-4-nitroanilide + H2O
Bz-Phe-Val-Arg + 4-nitroaniline
-
-
-
-
?
Meuchenia sp. insoluble muscle protein + H2O
hydrolyzed Meuchenia sp. insoluble muscle protein
-
-
-
-
?
N-alpha-benzyloxycarbonyl-Lys-p-nitrophenyl ester + H2O
N-alpha-benzyloxycarbonyl-Lys + p-nitrophenol
-
-
-
-
?
Nalpha-CBZ-L-lysine 4-nitrophenyl ester + H2O
Nalpha-CBZ-L-lysine + 4-nitrophenol
-
-
-
-
?
Pyr-Phe-Lys-4-nitroanilide + H2O
Pyr-Phe-Lys + 4-nitroaniline
-
isozyme SBA/b is about 3fold less active than isozyme SBA/a
-
?
tert-butyloxycarbonyl-Leu-Arg-Arg-4-methylcoumaryl-7-amide + H2O
tert-butyloxycarbonyl-Leu-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Tosyl-citrulline 4-nitroanilide + H2O
Tosyl-citrulline + 4-nitroaniline
-
-
-
-
?
Benzyloxycarbonyl-Arg-Arg 4-methylcoumarin 7-amide + H2O
Benzyloxycarbonyl-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Benzyloxycarbonyl-Arg-Arg 4-methylcoumarin 7-amide + H2O
Benzyloxycarbonyl-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
Benzyloxycarbonyl-Arg-Arg 4-methylcoumarin 7-amide + H2O
Benzyloxycarbonyl-Arg-Arg + 7-amino-4-methylcoumarin
-
convenient substrate for stem bromelain, scarcely affected by fruit bromelain
-
-
?
Benzyloxycarbonyl-Phe-Arg 4-methylcoumarin 7-amide + H2O
Benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Benzyloxycarbonyl-Phe-Arg 4-methylcoumarin 7-amide + H2O
Benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
casein + H2O
?
-
-
-
-
?
CD25 + H2O
?
-
bromelain proteolytically cleaved cell-surface CD25 from activated CD4+ T cells, a mechanism of action to exert therapeutic benefits in inflammatory conditions, overview
-
-
?
CD25 + H2O
?
-
soluble CD25is a therapeutic target in inflammation, autoimmunity and allergy
-
-
?
additional information
?
-
-
substrate conformation of N-acylglycine thioester substrates in the active site by resonance spectroscopy
-
-
?
additional information
?
-
-
enzyme reduces the amount of prostaglandin-E2 and substance P in vivo in inflammatory process in rats, while in vitro it induces an increase in the concentration of these inflammation mediators, thus the enzyme does not directly interact with the compounds, but has an antiinflammatory effect in vivo
-
?
additional information
?
-
-
bromelain from pineapple stem shows therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease, mechanism, overview. Bromelain primary long-term effect is abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion are correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128
-
-
?
additional information
?
-
-
bromelain possesses anti-inflammatory activity and reduces blood viscosity, prevents the aggregation of blood platelets, and improves ischemia-reperfusion injury, I/R, in a skeletal muscle model in adult Sprague-Dawley rats. The enzyme increases phosphorylation of Akt in rat heart both in the cytosolic and the nuclear fraction following I/R
-
-
?
additional information
?
-
-
CD4+ T cells retain the ability to divide after bromelain treatment
-
-
?
additional information
?
-
-
effects of orally administered bromelain in an ovalbumin-induced murine model of acute allergic airway disease in female C57BL/6J mice, bromelain causes decreased methacholine sensitivity, reduction in bronchoalveolar lavage eosinophils and interleukin-13 concentrations, as well as of CD19+ B cells and CD8+ T cells, as compared with controls, overview. Bromelain modulates lung lymphocytes during acute asthma
-
-
?
additional information
?
-
-
phosphorylation and consequent degradation of IkappaBalpha, the inhibitor of the nuclear importing sequences of NF-kappaB, is blocked by bromelain, which also shows anti-inflammatory, anti-invasive and anti-metastatic properties, anti-tumor-initiating effects of bromelain in 2-stage mouse skin tumorigenesis model, overview. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in Bcl-2, and bromelain inhibits DMBA-induced DNA alkylation damage, overview
-
-
?
additional information
?
-
-
bromelain proteolytically removes in vitro a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the human neutrophil chemoattractant IL-8 and its murine homologues. In vivo bromelain treatment generates a 50-85% reduction in human neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity, and bromelain treatment inhibits IL-8-stimulated migration of human neutrophils in vitro
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
CD25 + H2O
?
-
bromelain proteolytically cleaved cell-surface CD25 from activated CD4+ T cells, a mechanism of action to exert therapeutic benefits in inflammatory conditions, overview
-
-
?
additional information
?
-
-
enzyme reduces the amount of prostaglandin-E2 and substance P in vivo in inflammatory process in rats, while in vitro it induces an increase in the concentration of these inflammation mediators, thus the enzyme does not directly interact with the compounds, but has an antiinflammatory effect in vivo
-
?
additional information
?
-
-
bromelain from pineapple stem shows therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease, mechanism, overview. Bromelain primary long-term effect is abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion are correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128
-
-
?
additional information
?
-
-
bromelain possesses anti-inflammatory activity and reduces blood viscosity, prevents the aggregation of blood platelets, and improves ischemia-reperfusion injury, I/R, in a skeletal muscle model in adult Sprague-Dawley rats. The enzyme increases phosphorylation of Akt in rat heart both in the cytosolic and the nuclear fraction following I/R
-
-
?
additional information
?
-
-
CD4+ T cells retain the ability to divide after bromelain treatment
-
-
?
additional information
?
-
-
effects of orally administered bromelain in an ovalbumin-induced murine model of acute allergic airway disease in female C57BL/6J mice, bromelain causes decreased methacholine sensitivity, reduction in bronchoalveolar lavage eosinophils and interleukin-13 concentrations, as well as of CD19+ B cells and CD8+ T cells, as compared with controls, overview. Bromelain modulates lung lymphocytes during acute asthma
-
-
?
additional information
?
-
-
phosphorylation and consequent degradation of IkappaBalpha, the inhibitor of the nuclear importing sequences of NF-kappaB, is blocked by bromelain, which also shows anti-inflammatory, anti-invasive and anti-metastatic properties, anti-tumor-initiating effects of bromelain in 2-stage mouse skin tumorigenesis model, overview. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in Bcl-2, and bromelain inhibits DMBA-induced DNA alkylation damage, overview
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Dextran
dextran 70 kDa, for dextran, the crowding effect clearly depends on its molecular weight
L-3-carboxy-2,3-trans-epoxypropionylleucylamido(4-guanidino)butane
-
irreversible
sucrose
-
bromelain in the presence of 1 M sucrose is destabilized under thermal stress, the average melting temperature decrease by 5°C, additionally the enzyme is inactivated faster at 60°C
trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane
-
i.e. E-64, slow inactivation
trehalose
-
bromelain in the presence of 1 M trehalose is destabilized under thermal stress, the average melting temperature decrease by 7°C, additionally the enzyme is inactivated faster at 60°C
Ananas comosus bromelain inhibitor
-
competitive inhibition, several isoforms of the native double-chain protein, inhibition mechanism, structure-function relationship, structure modeling of inhibitor protein, bromelain inhibitor VI: PDB 1Bl6
-
Ananas comosus bromelain inhibitor
-
purified from stem, several isoforms of the native inhibitor protein consisting of multiple light and heavy chains, overview, 3D-structure model
-
SDS
-
SDS acts as a partial non-competitive inhibitor, 97% inhibition at 100 mM, detailed interaction study and inhibition mechanism, bromelain is partly resistant to SDS binding and denaturation, overview. SDS at submicellar level, below 5 mM, causes conformation change of bromelain leading to a stable entity
SDS
-
for native bromelain, SDS at 4 and 5 mg/ml causes a significant inhibition of 57% and 61%, respectively
additional information
crowders, such as dextran (D70) and polyethylene glycol (P12 and P20), destablize and deactivate native bromelain, absorption spectra in phosphate buffer, overview. PEGs tend to have different effects on different proteins depending upon the chemical nature of proteins, while for dextran, the crowding effect clearly depends on its molecular weight. PEG does not seem to follow the size-dependent crowding effect as in the case of dextran
-
additional information
stability of bromelain in the presence of EDTA and sodium benzoate
-
additional information
-
stability of bromelain in the presence of EDTA and sodium benzoate
-
additional information
the imidazolium-based ionic liquids, 1-butyl-3-methylimidazolium chloride, 1-butyl-3-methylimidazolium bromide, and 1-butyl-3-methylimidazolium iodide, act as destabilizers on stem bromelain, analysis using UV-visible spectroscopy, steady-state and thermal fluorescence, circular dichroism spectroscopy and dynamic light scattering measurements, overview
-
additional information
-
scarcely inhibited by chicken cystatin (amino acid sequence and implications for weak binding of cystatin)
-
additional information
-
scarcely inhibited by chicken cystatin (amino acid sequence and implications for weak binding of cystatin)
-
additional information
-
scarcely inhibited by chicken cystatin (amino acid sequence and implications for weak binding of cystatin)
-
additional information
-
scarcely inhibited by chicken cystatin (amino acid sequence and implications for weak binding of cystatin)
-
additional information
-
reversible inactivation of the protease in 10 mM Na-phosphate, pH 7.5 containing 5 mM of Na-tetrathionate, during purification, reactivation by 8 mM of DTT and 4 mM of EDTA in the same buffer at 25°C
-
additional information
-
gallic tannins or ellagic tannins show no inhibitory activity
-
additional information
-
grape skin and seed tannins exert uncompetitive inhibition
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
like ficin and unlike papain, bromelain does not possess a carboxyl group capable of enhancing the rate of reaction of the active-centre thiol group with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole
-
additional information
-
bromelain activator solution consists of 0.02 M EDTA and 0.05 M L-cysteine, pH 8.0
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.249
benzyl-Phe-Val-Arg-4-nitroanilide
-
tartaric buffer containing 12% ethanol, pH 3.2, 25°C, stem bromelain
200
benzoyl-L-Arg ethyl ester
-
enzyme form SB2, benzoyl-Gly ethyl ester, enzyme form SB1 and SB2
0.0074
benzyloxycarbonyl-Arg-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/b, pH 6.0, 25°C
0.0081
benzyloxycarbonyl-Arg-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/a, pH 6.0, 25°C
0.0554
benzyloxycarbonyl-Phe-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/a, pH 6.0, 25°C
0.0636
benzyloxycarbonyl-Phe-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/b, pH 6.0, 25°C
0.003
benzyloxycarbonyl-Phe-Val-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/b, pH 6.0, 25°C
0.0039
benzyloxycarbonyl-Phe-Val-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/a, pH 6.0, 25°C
0.03919
Bz-Phe-Val-Arg-4-nitroanilide
-
chitosan-immobilized enzyme, at pH 3.2 and 25°C
0.0495
Bz-Phe-Val-Arg-4-nitroanilide
-
chitosan-immobilized enzyme, in the presence of 12% (v/v) ethanol, at pH 3.2 and 25°C
0.05731
Bz-Phe-Val-Arg-4-nitroanilide
-
chitosan-immobilized enzyme, in the presence of 18% (v/v) ethanol, at pH 3.2 and 25°C
0.25
Bz-Phe-Val-Arg-4-nitroanilide
-
free enzyme, in the presence of 12% (v/v) ethanol, at pH 3.2 and 25°C
0.305
Bz-Phe-Val-Arg-4-nitroanilide
-
free enzyme, in the presence of 18% (v/v) ethanol, at pH 3.2 and 25°C
2.83
casein
-
poly(maleic anhydride)-modified enzyme, in 50 mM Tris-HCl buffer, pH 8.0, at 40°C
4.09
casein
-
pyromellitic anhydride-modified enzyme, in 50 mM Tris-HCl buffer, pH 8.0, at 40°C
additional information
additional information
-
kinetics of hydrolysis and influence of modifiers of hydrolysis of N-benzoyl-L-Ser methyl ester
-
additional information
additional information
-
kinetics of reaction of benzofuroxan, a thiol-specific reactivity probe with the enzyme
-
additional information
additional information
-
Km-for casein is 1.1 mg/ml for the native enzyme, 2 mg/ml for the enzyme covalently coupled to the CNBr-activated Sepharose and 0.54 mg/ml for enzyme affinity-bound to a Sepharose matrix precoupled with the lactin concanavalin A
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
20
benzyl-Phe-Val-Arg-4-nitroanilide
-
tartaric buffer containing 12% ethanol, pH 3.2, 25°C, stem bromelain
0.024
benzyloxycarbonyl-Arg-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/a, pH 6.0, 25°C
0.04
benzyloxycarbonyl-Arg-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/b, pH 6.0, 25°C
0.49
benzyloxycarbonyl-Phe-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/a, pH 6.0, 25°C
0.56
benzyloxycarbonyl-Phe-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/b, pH 6.0, 25°C
6.08
benzyloxycarbonyl-Phe-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/b, pH 6.0, 25°C
5.1
benzyloxycarbonyl-Phe-Val-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/a, pH 6.0, 25°C
6.4
benzyloxycarbonyl-Phe-Val-Arg-NH-4-methylcoumarin 7-amide
-
isozyme SBA/b, pH 6.0, 25°C
0.29
Bz-Phe-Val-Arg-4-nitroanilide
-
chitosan-immobilized enzyme, in the presence of 12% (v/v) ethanol, at pH 3.2 and 25°C
0.399
Bz-Phe-Val-Arg-4-nitroanilide
-
chitosan-immobilized enzyme, in the presence of 18% (v/v) ethanol, at pH 3.2 and 25°C
0.461
Bz-Phe-Val-Arg-4-nitroanilide
-
chitosan-immobilized enzyme, at pH 3.2 and 25°C
20.03
Bz-Phe-Val-Arg-4-nitroanilide
-
free enzyme, in the presence of 12% (v/v) ethanol, at pH 3.2 and 25°C
21.45
Bz-Phe-Val-Arg-4-nitroanilide
-
free enzyme, in the presence of 18% (v/v) ethanol, at pH 3.2 and 25°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
activity of glycosylated and deglycosylated enzyme at different temperatures and pH 7.0, and at different pH-values and 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.6
7.5
7.5
-
native enzyme, enzyme covalently coupled to the CNBr-activated Sepharose and enzyme affinity-bound to a Sepharose matrix precoupled with the lactin concanavalin A
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 11
-
pH 5.0: native enzyme shows about 25% of maximal activity, enzyme covalently coupled to the CNBr-activated Sepharose shows about 30% of maximal activity, enzyme affinity-bound to a Sepharose matrix precoupled with the lactin concanavalin A shows about 35% of maximal activity, pH 11: native enzyme shows about 25% of maximal activity, enzyme covalently coupled to the CNBr-activated Sepharose shows about 30% of maximal activity, enzyme affinity-bound to a Sepharose matrix precoupled with the lactin concanavalin A shows about 60% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60
60
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60 - 80
bromelain from the leaves shows higher activity between 60 and 80°C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
-
30265, 30266, 30267, 30273, 30274, 30275, 30276, 30277, 30278, 30279, 30280, 30281, 30282, 30283, 30284, 30285, 30286, 30287, 30288, 30289, 30290, 30291, 30292, 30293, 30294, 30295, 30296, 30297, 30298, 650260, 650459, 651136, 651753, 652582, 653423, 664145, 664339, 664432, 665082, 665207, 665217, 677476, 680253, 680545, 681487, 682476, 696470, 697088, 697421, 697783, 717487, 731526, 731527, 731838, 731938, 732431, 732495, 732755, 752380, 752632
additional information
analysis of bromelain activity in different Ananas comosus parts and tissues, overview
additional information
-
analysis of bromelain activity in different Ananas comosus parts and tissues, overview
additional information
-
determination of bromelain protease activity in different tissues of pineapple of the Morris variety, overview. The flesh of the pineapple fruit is the largest portion of tissue, followed by peel, core, stem, and crown
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
additional information
physiological function
antiproliferative effect of bromelain from different tissues against B16F10 murine melanoma cells, overview
physiological function
the highest anti-proliferation of the freeze-dried and the spray-dried bromelain versus A549 cells are observed with IC50 values of 0.0183 and 0.0264 mg/ml, respectively. For apoptotic induction, the highest activity of the freeze-dried and the spray-dried bromelain is observed on KB (7.53%) and A549 (6.29%) cell lines, respectively. Stem bromelain exhibits apoptotic induction activity on DU145, HT-29, A549, KB, HeLa, and HuTu-80 cells, but not on Hep-G2 cells
physiological function
-
bromelain increases expression of p53 as well as Bax in mouse skin papillomas, at the same time, bromelain decreases the activity of cell survival regulators such as Akt and Erk thus promoting apoptotic cell death in tumors. Bromelain reduces CD44 on the surface of mouse and human tumor cells accompanied by diminished cancer cell invasion and substrate attachment as well as by attenuation of de novo protein synthesis. Bromelain can stimulate the innate immune system by activating neutrophils to produce reactive oxygen species
physiological function
-
bromelain decreases neutrophil interactions with P-selectin in vitro by proteolytic cleavage of P-selectin glycoprotein ligand-1
physiological function
-
chelating potential of stem bromelain for combating lead toxicity and oxidative stress, protective efficacy of stem bromelain against lead-induced toxicity in male Wistar rats, overview. Co-administration of stem bromelain with lead markedly reduces the lead accumulation in the kidney and spleen. The treatment of stem bromelain also reduces the serum malonaldehyde levels in the group exposed to lower dose of lead and serum triglyceride level in the group exposed to higher dose of lead. The lead-induced modulated levels of serum ALT and AST are also alleviated by bromelain treatment
additional information
analysis of of macromolecular crowding on stem bromelain, i.e. effects of dextran (D70) and polyethylene glycol (P12 and P20) on native bromelain structure, by combining the results of absorption, circular dichroism, fluorescence and activity studies, detailed overview. The overall effect of the crowders on the enzyme is destabilization and deactivation. Molecular docking simulation of bromelain with PEG and dextran
additional information
comparative structural analysis of fruit and stem bromelain from Ananas comosus, structure homology modelling, model domain organisation, overview. The proteolytic fraction of pineapple stem is termed stem bromelain, while the one presents in the fruit is known as fruit bromelain (EC 3.4.22.33). NCBI conserved domain analysis reveals two domains of fruit and stem bromelain: cathepsin propeptide inhibitor (I29) and peptidase C1
additional information
-
comparative structural analysis of fruit and stem bromelain from Ananas comosus, structure homology modelling, model domain organisation, overview. The proteolytic fraction of pineapple stem is termed stem bromelain, while the one presents in the fruit is known as fruit bromelain (EC 3.4.22.33). NCBI conserved domain analysis reveals two domains of fruit and stem bromelain: cathepsin propeptide inhibitor (I29) and peptidase C1
additional information
effects of bromelain on the pro-wound healing activities and the regenerative properties of mesenchymal stem cells, overview. The combination of bromelain and dexamethasone sodium phosphate induces a great activation of mesenchymal stem cells with an increase in hyaluronan and collagen production and antiinflammatory cytokines release, real-time polymerase chain reaction analysis of extracellular matrix proteins and remodeling enzymes in human mesenchymal stem cells, overview
additional information
-
effects of bromelain on the pro-wound healing activities and the regenerative properties of mesenchymal stem cells, overview. The combination of bromelain and dexamethasone sodium phosphate induces a great activation of mesenchymal stem cells with an increase in hyaluronan and collagen production and antiinflammatory cytokines release, real-time polymerase chain reaction analysis of extracellular matrix proteins and remodeling enzymes in human mesenchymal stem cells, overview
additional information
three-dimensional structure homology modelling of stem bromelain using the procaricain enzyme structure as template, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). BROM2_ANACO
212
0
22831
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
23000
26000
28000
28400
-
Ananas comosus, sedimentation velocity and equilibrium ultracentrifugation experiments
33000
-
Ananas comosus, determination from sedimentation and diffusion coefficient
additional information
23000
-
x * 23000, Ananas comosus, SDS-PAGE, 2 chains of MW 15000 and 8500 upon reduction with HS(CH2)2OH
28000
-
Ananas comosus, enzyme form SB1 and SB2, sedimentation equilibrium method
additional information
-
isolation and alignment of 3 peptides obtained by means of cyanogen bromide cleavage
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
?
-
x * 23000, Ananas comosus, SDS-PAGE, 2 chains of MW 15000 and 8500 upon reduction with HS(CH2)2OH
monomer
-
1 * 23550-27900, isozyme SBA/a, mass spectroscopy and SDS-PAGE, 1 * 23560-27800, isozyme SBA/b, mass spectroscopy and SDS-PAGE
additional information
comparative structural analysis of fruit and stem bromelain from Ananas comosus
additional information
-
comparative structural analysis of fruit and stem bromelain from Ananas comosus
additional information
secondary and tertiary structure prediction from sequence with UniProt ID F1KD58, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
enzyme form F4 and F5 contain fucose, N-acetylglucosamine, xylose and mannose in the ratio of 1.0:2.0:1.0:2.0, but only 50% of the proteins seem to be glycosylated, enzyme form F9 is unglycosylated
glycoprotein
-
carbohydrate content: 4.3% (enzyme form SBB1), 3.6% (enzyme form SBB2), 3.5% (enzyme form SBB3), 8.2% (enzyme form SBA), enzyme form SBB4 and SBB5 contain no carbohydrate
glycoprotein
-
carbohydrate composition: molar ratio of mannose:xylose:fucose is 2.43:1.0:1.01 (enzyme form SB1), 2.55:1.17:0.92 (enzyme form SB2)
glycoprotein
-
neutral sugar content: 4.89% (enzyme form SB1), 5.24% (enzyme form SB2)
glycoprotein
-
both isozymes are highly glycosylated, isozyme SBA/a is about 2fold more glycosylated than isozyme SBA/b, glycoslyation composition
glycoprotein
-
glycosylation stabilizes the enzyme, enzyme contains a single hetero-oligosaccharide unit per molecule, deglycosylated enzyme shows decreased activity
glycoprotein
-
contains a single oligosaccharide chain attached to the polypeptide
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.8 - 2
-
stem bromelain at pH 2.0 is maximally unfolded and characterized by significant loss of secondary structure (about 80%) and almost complete loss of tertiary contacts, at pH 0.8 a molten globule state is observed with secondary structure content similar to that of native protein but no tertiary structure
680545
3.2 - 7
-
stem bromelain solubilized at pH 7.0 and at pH 3.2 retains, after 16 h at 256°C, 10 and 40% of the initial activity, respectively
731526
5.5 - 10
-
stem bromelain is fully resistant against urea around neutral pH (5.5 to 10.0) and unfolds only below pH 5.0
707537
7 - 10
-
from pH 7.0 to 10.0, the protein's secondary structure remains the same, although a slight loss of tertiary structure is observed. Above pH 10.0, there is a significant and irreversible loss of secondary and tertiary structure. At pH 10.0, SBM shows a significant increase in 8-anilino-1-naphthalene-sulfonate binding relative to the native state. No significant loss of activity is observed up to pH 10.0, beyond which there is an irreversible loss of activity
707283
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
70
soluble enzyme retains 53% activity after incubation at 70°C, immobilized enzyme retains over 70% activity after incubation at 70°C
100
-
recombinant bromelain shows no activity after 30 min of incubation at 100°C
4
-
recombinant protein stored at 4°C shows a loss in enzymatic activity. The percentage loss in recombinant bromelain enzymatic activity is 27.5%
45
60
additional information
60
-
100 min, native enzyme loses 80% of initial activity, enzyme covalently coupled to the CNBr-activated Sepharose loses 70% of the initial activity, enzyme affinity-bound to a Sepharose matrix precoupled with the lactin concanavalin A loses 50% of initial activity
60
-
native bromelain rapidly loses activity at 60°C and retains only about 10% of the initial activity after incubation for 180 min, about 70% and 58% of the initial activity is retained by uniformly coupled and randomly coupled N-isopropylacrylamide-enzyme preparations, respectively, after 180 min incubation at 60°C
60
-
the native enzyme retains 20% of the initial activity after incubation at 60°C
additional information
-
thermal denaturation is consistent with an irreversible two-state model
additional information
-
immobilization offers more resistance to denaturation particularly at 60°C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dextran (D70) and polyethylene glycol (P12 and P20) destablize native bromelain structure
immobilization on amino-Sepharose leads to higher proteolytic activity and remarkably enhanced thermal stability as compared to soluble bromelain and that coupled to CNBr- activated Sepharose
the imidazolium-based ionic liquids, 1-butyl-3-methylimidazolium chloride, 1-butyl-3-methylimidazolium bromide, and 1-butyl-3-methylimidazolium iodide, act as destabilizers on stem bromelain, analysis using UV-visible spectroscopy, steady-state and thermal fluorescence, circular dichroism spectroscopy and dynamic light scattering measurements, overview. The destabilization behaviour increases with increase in the chaotropicity or decrease in the kosmotropicity of the anion of the ionic liquid
bromelain immobilized to IDA-Sepharose 6B matrix loaded with Cu2+, Ni2+ and Zn2+ is more resistant to thermal inactivation, as evidenced by retention of over 50% activity after incubation at 60°C
-
denaturation in guanidine hydrochloride, the deglycosylated enzyme is more sensitive than the glycosylated one, midpoints of transition are at 2.28 M and 2.86 M, respectively
-
enzymatic activity of bromelain remains uninfluenced by the immobilization of heparin on it
-
enzyme affinity-bound to a Sepharose matrix precoupled with the lactin concanavalin A is more stable to thermal inactivation than native enzyme or enzyme covalently coupled to the CNBr-activated Sepharose
-
glutaraldehyde-crosslinked bromelain has comparable activity to the native enzyme, is more stable against urea, guanidine hydrochloride and temperature-induced inactivation and exhibit better storage ability compared to the unmodified protease
-
glycerol and sorbitol are acting as stabilizers at all concentrations while sucrose and trehalose are destabilizers at lower concentrations, however, act as stabilizers at higher concentrations. Urea and guanidine hydrochloride are denaturants except at lower concentrations
-
immobilized bromelain shows a higher half-life respect to the free enzyme. The addition of free cysteine during immobilization phase, improves bromelain half-life more than 4folds
-
increase in ionic strength by addition of salts results in folded structures somewhat different from the native enzyme. Salt-induced intermediates are characterized by increase in helical content and a significantly reduced exposure of hydrophobic clusters relative to the state at pH 2.0. Salt-induced state shows non-cooperative thermal denaturation alcohol-induced intermediates of the enzyme exhibit increased helical content. Alcohol-induced state shows a cooperative thermal transition
-
poly(ethylene glycol)-400-induced state has characteristics of molten globule, higher molecular weight poly(ethylene glycol)s cause unfolding of the acid unfolded state
-
Stem bromelain covalently coupled to a thermosensitive polymer of N-isopropylacrylamide either through the amino groups of the enzyme (randomly coupled) or via the lone oligosaccharide chain (uniformly coupled) shows better thermostability. The enzyme coupled via the oligosaccharide chain exhibits better access to the substrate casein as compared to the preparation in which the amino groups formed the point of contact between the enzyme and the polymer.
-
the low bromelain activity, particularly in the upper portion of the murine gastrointestinal tract, following oral administration, suggests that extensive gastric inactivation of bromelain may occur in vivo. When formulated in antacid, oral bromelain retains substantial proteolytic activity throughout the gastrointestinal tract (of mice)
-
the pyromellitic anhydride- and poly(maleic anhydride)-modified bromelain does not lose its activity significantly
-
treatment with 10-30% (v/v) 1,1,1,3,3,3-hexafluoroisopropanol induces the partially folded intermediate to adopt much of the native proteins secondary structure, but only a rudimentary tertiary structure, characteristic of the molten globule state. Addition of slightly higher concentrations of 1,1,1,3,3,3-hexafluoroisopropanol causes transformation from an alpha-helix to a beta-sheet and induces formation of a compact nonnative structure
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
2,2,2-trifluoroethanol
-
the enhanced binding of 1-anilino-8-naphthalene sulfonic acid to the specific/pre-molten globule (SMG) state of stem bromelain upon addition of 30% 2,2,2-trifluoroethanol suggests the presence of a large number of solvent-accessible non-polar clusters in the treated SMG. The formation of an molten globe (MG)-like state characterized by disordered side chain interactions but with considerable secondary structure when the specific/pre-molten globule (SMG) state of stem bromelain is subjected to 30% 2,2,2-trifluoroethanol (TFE). The TFE-induced MG conformation at alkaline pH could represent the conformation that allows stem bromelain to traverse membranes
Ethanol
guanidine-HCl
urea
Ethanol
-
enzyme stabilized in 60-70% ethanol is non-functional, but retains all the elements of secondary structure
guanidine-HCl
-
6 M guanidine-HCl denatured state of stem bromelain is enzymatically inactive
urea
-
stem bromelain is fully resistant against urea around neutral pH (5.5 to 10.0) and unfolds only below pH 5.0
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
oxidation of the active site thiol leads to the corresponding sulfinic acid, which is catalytically inactive, irreversible oxidative degradation may lead to reduced activity of isozyme SBA/b with substrate Pyr-Phe-Lys-4-nitroanilide
-
653021
photosensitized oxidation of stem bromelain in the presence of methylene blue results in partial loss of the enzymatic activity even if the essential sulfhydryl group is protected against oxidation
-
30274, 30286
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
bromelain is precipitated from the pineapple stem juice by 95% v/v ethanol and then freeze-dried or spray-dried to get the dry powder
bromelain from pineapple stem and skin are recovered by a PEG 4000/phosphate aqueous two-phase systems (ATPs) liquid-liquid extraction
-
carboxymethylcellulose 52 column chromatography, and Sephadex G-100 gel filtration
-
native enzyme from stem, reversible inactivation of the protease in 10 mM Na-phosphate, pH 7.5 containing 5 mM of Na-tetrathionate, during purification, reactivation by 8 mM of DTT and 4 mM of EDTA in the same buffer at 25°C, followed by gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloned into the pENTR/TEV/D-TOPO vector, then sub-cloned into the pDEST17 expression vector. Expression in Escherichia coli BL21
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
pharmacology
agriculture
-
a concentration of 0.0003 mM of bromelain is sufficient for 90% growth inhibition of Fusarium verticillioides. Bromelain also inhibits the growth of Fusarium oxysporum f. sp. melonis and Fuarium proliferatum. The enzyme shows a potential use as an effective agent for crop protection
food industry
medicine
medicine
bromelain has gained wide acceptance and compliance as a phytotherapeutical drug. Cysteine proteases in pineapple (Ananas comosus) plants are phytotherapeutical agents that demonstrate anti-edematous, anti-inflammatory, anti-thrombotic and fibrinolytic activities
medicine
potential of the stem bromelain to be developed as an active compound for lung cancer therapy because of its high anti-proliferation and apoptosis-induction activity in A549 cells
pharmacology
bromelain is pharmacologically active against B16F10 melanoma cells with complete inhibition of tumor cell proliferation in vitro
pharmacology
in vitro anti-cancer activity (anti-proliferation and apoptosis induction) comparison of the freeze-dried and spray-dried bromelain from pineapple stems
food industry
-
stem bromelain immobilized on chitosan beads without glutaraldehyde yields a food-safe biocatalyst for unstable real wine future application
food industry
-
the immobilized stem bromelain has productive biotechnological applications in wine-making
medicine
-
oral bromelain may potentially modify inflammation within the gastrointestinal tract via local proteolytic activity within the colonic microenvironment
medicine
-
the complex between stem bromelain and polyclonal Fab* monomer can serve as a model with potential in vivo and industrial application especially in homogenous reaction phases and development of subunit vaccines owing to preponderance of hydrophobic interaction and better diffusion potential of Fab' than of intact IgG
medicine
-
bromelain shows antitumorigenic potential by inducing apoptosis-related proteins along with inhibition of nuclear factor-kappa B driven cyclooxygenase-2 expression by blocking the mitogen-activated protein kinase and Akt/protein kinase B signaling in 7,12-dimethylbenz(a)anthracene-12-O-tetradecanoylphorbol-13-acetate-induced mouse skin tumors
medicine
-
stem bromelain triggers an Akt-dependent survival pathway in the heart, revealing a mechanism of cardioprotective action and a potential therapeutic target against ischemia/perfusion injury
medicine
-
bromelain from pineapple stem shows therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease, mechanism, overview. Bromelain primary long-term effect is abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion are correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128
medicine
-
bromelain possesses anti-inflammatory activity and reduces blood viscosity, prevents the aggregation of blood platelets, and improves ischemia-reperfusion injury, I/R, in a skeletal muscle model in adult Sprague-Dawley rats. The enzyme increases phosphorylation of Akt in rat heart both in the cytosolic and the nuclear fraction following I/R
medicine
-
effects of orally administered bromelain in an ovalbumin-induced murine model of acute allergic airway disease in female C57BL/6J mice, bromelain causes decreased methacholine sensitivity, reduction in bronchoalveolar lavage eosinophils and interleukin-13 concentrations, as well as of CD19+ B cells and CD8+ T cells, as compared with controls, overview. Bromelain modulates lung lymphocytes during acute asthma
medicine
-
bromelain has anti-cancer activity, as well as antithrombotic, fibrinolytic, antiedematous, and burn debridement properties
medicine
-
the nonnative form of SBM shows only a fraction of the native protein's enzymatic activity but is more effective at inhibiting cell growth and displays better antitumorigenic properties than native SBM
medicine
-
bromelain relieves osteoarthritis. Bromelain is used as an adjuvant therapeutic approach in the treatment of chronic inflammatory, malignant, and autoimmune diseases. Bromelain prevents or minimizes the severity of angina pectoris and transient ischemic attack. Bromelain influences blood coagulation by increasing the serum fibrinolytic ability and by inhibiting the synthesis of fibrin. Bromelain counteracts some of the effects of certain intestinal pathogens like Vibrio cholera and Escherichia coli, whose enterotoxin causes diarrhea. The anticancerous activity of bromelain is due to its direct impact on cancer cells and their microenvironment, as well as on the modulation of immune, inflammatory, and haemostatic systems. Bromelain is used for treating acute inflammation and sports injuries. Bromelain applied as a cream (35% bromelain in a lipid base) can be beneficial for debridement of necrotic tissue and acceleration of healing
medicine
bromelain exhibits various fibrinolytic, anti-edematous, anti-thrombotic, and anti-inflammatory activities supporting its application for many therapeutic benefits. Effects of bromelain on the pro-wound healing activities and the regenerative properties of mesenchymal stem cells. The combined use of bromelain and dexamethasone sodium phosphate stimulated the pro-wound healing activities and the regenerative properties of mesenchymal stem cells better than bromelain and dexamethasone alone
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rowan, A.D.; Buttle, D.J.; Barrett, A.J.
Ananain: a novel cysteine proteinase found in pineapple stem
Arch. Biochem. Biophys.
267
262-270
1988
Ananas comosus
Rowan, A.D.; Buttle, D.J.; Barrett, A.J.
The cysteine proteinases of the pineapple plant
Biochem. J.
266
869-875
1990
Ananas comosus
Rowan, A.D.; Buttle, D.J.
Pineapple cysteine endopeptidases
Methods Enzymol.
244
555-568
1994
Ananas comosus
Heinrikson, R.L.; Kezdy, F.J.
Acidic cysteine protease inhibitors from pineapple stem
Methods Enzymol.
45
740-751
1976
Ananas comosus
Ritonja, A.; Rowan, A.D.; Buttle, D.J.; Rawlings, N.D.; Turk, V.; Barrett, A.J.
Stem bromelain: amino acid sequence and implications for weak binding of cystatin
FEBS Lett.
247
419-424
1989
Ananas comosus
Ota, S.; Horie, K.; Hagino, F.; Hashimoto, C.; Date, H.
Fractionation and some properties of the proteolytically active components of bromelains in the stem and the fruit of the pineapple plant
J. Biochem.
71
817-830
1972
Ananas comosus
Ota, S.; Muta, E.; Katahira, Y.; Okamoto, Y.
Reinvestigation of fractionation and some properties of the proteolytically active components of stem and fruit bromelains
J. Biochem.
98
219-228
1985
Ananas comosus
Rowan, A.D.; Brzin, J.; Buttle, D.J.; Barrett, A.J.
Inhibition of cysteine proteinases by a protein inhibitor from potato
FEBS Lett.
269
328-330
1990
Ananas comosus
Arroyo-Reyna, A.; Hernandez-Arana, A.
The thermal denaturation of stem bromelain is consistent with an irreversible two-state model
Biochim. Biophys. Acta
1248
123-128
1995
Ananas comosus
Goto, K.; Murachi, T.; Takahashi, N.
Structural studies on stem bromelain isolation, characterization and alignment of the cyanogen bromide fragments
FEBS Lett.
62
93-95
1976
Ananas comosus
Silverstein, R.M.; Kezdy, F.J.
Characterization of the pineapple stem proteases (bromelains)
Arch. Biochem. Biophys.
167
678-686
1975
Ananas comosus
Wharton, C.W.
The structure and mechanism of stem bromelain. Evaluation of the homogeneity of purified stem bromelain, determination of the molecular weight and kinetic analysis of the bromelain-catalysed hydrolysis of N-benzyloxycarbonyl-L-phenylalanyl-L-serine methyl ester
Biochem. J.
143
575-586
1974
Ananas comosus
Wharton, C.W.; Cornish-Bowden, A.; Brocklehurst, K.; Crook, E.M.
Kinetics of the hydrolysis of N-benzoyl-L-serine methyl ester catalysed by bromelain and by papain. Analysis of modifier mechanisms by lattice nomography, computational methods of parameter evaluation for substrate-activated catalyses and consequences of postulated non-productive binding in bromelain- and papain-catalysed hydrolyses
Biochem. J.
141
365-381
1974
Ananas comosus
Minami, Y.; Doi, E.; Hata, T.
Fractionation, purification, and some properties of proteolytic enzymes from stem bromelain
Agric. Biol. Chem.
35
1419-1430
1971
Ananas comosus
-
Murachi, T.; Tsudzuki, T.; Okumura, K.
Photosensitized inactivation of stem bromelain. Oxidation of histidine, methionine, and tryptophan residues
Biochemistry
14
249-255
1975
Ananas comosus
Takahashi, N.; Yasuda, Y.; Goto, K.; Miyake, T.; Murachi, T.
Multiple molecular forms of stem bromelain. Isolation and characterization of two closely related components, SB1 and SB2
J. Biochem.
74
355-373
1973
Ananas comosus
Carey, P.R.; Ozaki, Y.; Storer, A.C.
Comparison of the substrate conformations in the active sites of papain, chymopapain, ficin and bromelain by resonance Raman spectroscopy
Biochem. Biophys. Res. Commun.
117
725-731
1983
Ananas comosus
Gray, C.J.; Boukouvalas, J.; Szawelski, R.J.; Wharton, C.W.
Benzyloxycarbonylphenylalanylcitrulline p-nitroanilide as a substrate for papain and other plant cysteine proteinases
Biochem. J.
219
325-328
1984
Ananas comosus
Shipton, M.; Brocklehurst, K.
Benzofuroxan as a thiol-specific reactivity probe. Kinetics of its reactions with papain, ficin, bromelain and low-molecular-weight thiols
Biochem. J.
167
799-810
1977
Ananas comosus
Shipton, M.; Stuchbury, T.; Brocklehurst, K.
4-Chloro-7-nitrobenzo-2-oxa-1,3-diazole as a reactivity probe for the investigation of the thiol proteinases. evidence that ficin and bromelain may lack carboxyl groups conformationally equivalent to that of aspartic acid-158 of papain
Biochem. J.
159
235-244
1976
Ananas comosus
Bobb, D.
Isolation of stem bromelain by affinity chromatography and its partial characterization by gel electrophoresis
Prep. Biochem.
2
347-354
1972
Ananas comosus
Lenarcic, B.; Ritonja, A.; Turk, B.; Dolenc, I.; Turk, V.
Characterization and structure of pineapple stem inhibitor of cysteine proteinases
Biol. Chem. Hoppe-Seyler
373
459-464
1992
Ananas comosus
Dickson, S.R.; Bickerstaff, G.F.
Properties of immobilized bromelain
Biochem. Soc. Trans.
20
23S
1992
Ananas comosus
Harrach, T.; Eckert, K.; Schulze-Forster, K.; Nuck, R.; Grunow, D.; Maurer, H.R.
Isolation and partial characterization of basic proteinases from stem bromelain
J. Protein Chem.
14
41-52
1995
Ananas comosus
Suh, H.J.; Lee, H.; Cho, H.Y.; Yang, H.C.
Purification and characterization of bromelain isolated from pineapple
Han'guk Nonghwa Hakhoechi
35
300-307
1992
Ananas comosus
-
Ko, Y.H.; Kang, Y.J.
Isolation and partial characterization of proteolytic enzymes from stems of pineapples cultivated in Cheju Island
Nonmunjip-Cheju Taehakkyo, Chayon Kwahakpyon
31
137-142
1990
Ananas comosus
-
Goto, K.; Takahashi, N.; Murachi, T.
Structural studies on stem bromelain. Cyanogen bromide cleavage and amino acid sequence of carboxyl-terminal half of the molecule
Int. J. Pept. Protein Res.
15
335-341
1980
Ananas comosus
Rasheedi, S.; Haq, S.K.; Khan, R.H.
Guanidine hydrochloride denaturation of glycosylated and deglycosylated stem bromelain
Biochemistry
68
1097-1100
2003
Ananas comosus
Hatano, K.; Sawano, Y.; Tanokura, M.
Structure-function relationship of bromelain isoinhibitors from pineapple stem
Biol. Chem.
383
1151-1156
2002
Ananas comosus
Haq, S.K.; Rasheedi, S.; Khan, R.H.
Characterization of a partially folded intermediate of stem bromelain at low pH
Eur. J. Biochem.
269
47-52
2002
Ananas comosus
Hatano, K.; Tanokura, M.; Takahashi, K.
The amino acid sequences of isoforms of the bromelain inhibitor from pineapple stem
J. Biochem.
124
457-461
1998
Ananas comosus
Khan, R.H.; Rasheedi, S.; Haq, S.K.
Effect of pH, temperature and alcohols on the stability of glycosylated and deglycosylated stem bromelain
J. Biosci.
28
709-714
2003
Ananas comosus
Harrach, T.; Eckert, K.; Maurer, H.R.; Machleidt, I.; Machleidt, W.; Nuck, R.
Isolation and characterization of two forms of an acidic bromelain stem proteinase
J. Protein Chem.
17
351-361
1998
Ananas comosus
Gaspani, L.; Limiroli, E.; Ferrario, P.; Bianchi, M.
In vivo and in vitro effects of bromelain on PGE2 and SP concentrations in the inflammatory exudate in rats
Pharmacology
65
83-86
2002
Ananas comosus
Gupta, P.; Saleemuddin, M.; Khan, R.H.
Hydrophobic interactions are the prevalent force in bromelain:Fab complex
Biochemistry
71
S31-S37
2006
Ananas comosus
-
Ahmad, B.; Ansari, M.A.; Sen, P.; Khan, R.H.
Low versus high molecular weight poly(ethylene glycol)-induced states of stem bromelain at low pH: stabilization of molten globule and unfolded states
Biopolymers
81
350-359
2006
Ananas comosus
Gupta, P.; Saleemuddin, M.
Bioaffinity based oriented immobilization of stem bromelain
Biotechnol. Lett.
28
917-922
2006
Ananas comosus
Rowan, A.D.
Stem bromelain
Handbook of proteolytic enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , eds. ) Academic Press
2
1136-1137
2004
Ananas comosus
-
Hale, L.P.
Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice
Int. Immunopharmacol.
4
255-264
2004
Ananas comosus
Haq, S.K.; Rasheedi, S.; Sharma, P.; Ahmad, B.; Khan, R.H.
Influence of salts and alcohols on the conformation of partially folded intermediate of stem bromelain at low pH
Int. J. Biochem. Cell Biol.
37
361-374
2005
Ananas comosus
Juhasz, B.; Thirunavukkarasu, M.; Pant, R.; Zhan, L.; Penumathsa, S.V.; Secor, E.R.; Srivastava, S.; Raychaudhuri, U.; Menon, V.P.; Otani, H.; Thrall, R.S.; Maulik, N.
Bromelain induces cardioprotection against ischemia-reperfusion injury through Akt/FOXO pathway in rat myocardium
Am. J. Physiol. Heart Circ. Physiol.
294
H1365-H1370
2008
Ananas comosus
Anwar, T.; Ahmad, B.; Younus, H.
Cross-linked stem bromelain: A more stabilized active preparation
Biocatal. Biotransform.
25
453-458
2007
Ananas comosus
-
Mahmood, R.; Saleemuddin, M.
Additional stabilization of stem bromelain coupled to a thermosensitive polymer by uniform orientation and using polyclonal antibodies
Biochemistry (Moscow)
72
307-312
2007
Ananas comosus
Grabovac, V.; Bernkop-Schnuerch, A.
Improvement of the intestinal membrane permeability of low molecular weight heparin by complexation with stem bromelain
Int. J. Pharm.
326
153-159
2006
Ananas comosus
Ahmad, B.; Khan, R.H.
Studies on the acid unfolded and molten globule states of catalytically active stem bromelain: A comparison with catalytically inactive form
J. Biochem.
140
501-508
2006
Ananas comosus
Ahmad, B.; Shamim, T.A.; Haq, S.K.; Khan, R.H.
Identification and characterization of functional intermediates of stem bromelain during urea and guanidine hydrochloride unfolding
J. Biochem.
141
251-259
2007
Ananas comosus
Gupta, P.; Maqbool, T.; Saleemuddin, M.
Oriented immobilization of stem bromelain via the lone histidine on a metal affinity support
J. Mol. Catal. B
45
78-83
2007
Ananas comosus
-
Baez, R.; Lopes, M.T.; Salas, C.E.; Hernandez, M.
In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain
Planta Med.
73
1377-1383
2007
Ananas comosus
Habib, S.; Khan, M.A.; Younus, H.
Thermal destabilization of stem bromelain by trehalose
Protein J.
26
117-124
2007
Ananas comosus
Khatoon, H.; Younus, H.; Saleemuddin, M.
Stem bromelain: an enzyme that naturally facilitates oriented immobilization
Protein Pept. Lett.
14
233-236
2007
Ananas comosus (P14518)
Kalra, N.; Bhui, K.; Roy, P.; Srivastava, S.; George, J.; Prasad, S.; Shukla, Y.
Regulation of p53, nuclear factor kappaB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin
Toxicol. Appl. Pharmacol.
226
30-37
2008
Ananas comosus
Bhattacharya, R.; Bhattacharyya, D.
Resistance of bromelain to SDS binding
Biochim. Biophys. Acta
1794
698-708
2009
Ananas comosus
Bhui, K.; Prasad, S.; George, J.; Shukla, Y.
Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway
Cancer Lett.
282
167-176
2009
Ananas comosus
Fitzhugh, D.J.; Shan, S.; Dewhirst, M.W.; Hale, L.P.
Bromelain treatment decreases neutrophil migration to sites of inflammation
Clin. Immunol.
128
66-74
2008
Ananas comosus
Secor, E.R.; Carson, W.F.; Singh, A.; Pensa, M.; Guernsey, L.A.; Schramm, C.M.; Thrall, R.S.
Oral bromelain attenuates inflammation in an ovalbumin-induced murine model of asthma
Evid. Based. Complement Alternat. Med.
5
61-69
2008
Ananas comosus
Secor, E.R.; Singh, A.; Guernsey, L.A.; McNamara, J.T.; Zhan, L.; Maulik, N.; Thrall, R.S.
Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro
Int. Immunopharmacol.
9
340-346
2009
Ananas comosus
Dave, S.; Mahajan, S.; Chandra, V.; Dkhar, H.K.; Sambhavi, H.K.; Gupta, P.
Specific molten globule conformation of stem bromelain at alkaline pH
Arch. Biochem. Biophys.
499
26-31
2010
Ananas comosus
Ahmad, B.; Rathar, G.M.; Varshney, A.; Khan, R.H.
pH-Dependent urea-induced unfolding of stem bromelain: Unusual stability against urea at neutral pH
Biochemistry
74
1337-1343
2009
Ananas comosus
Chobotova, K.; Vernallis, A.B.; Majid, F.A.
Bromelain's activity and potential as an anti-cancer agent: Current evidence and perspectives
Cancer Lett.
290
148-156
2010
Ananas comosus
Salampessy, J.; Phillips, M.; Seneweera, S.; Kailasapathy, K.
Release of antimicrobial peptides through bromelain hydrolysis of leatherjacket (Meuchenia sp.) insoluble proteins
Food Chem.
120
556-560
2010
Ananas comosus
Dave, S.; Dkhar, H.K.; Singh, M.P.; Gupta, G.; Chandra, V.; Mahajan, S.; Gupta, P.
Hexafluoroisopropanol-induced helix-sheet transition of stem bromelain: correlation to function
Int. J. Biochem. Cell Biol.
42
938-947
2010
Ananas comosus
Xue, Y.; Wu, C.; Branford-White, C.; Ning, X.; Nie, H.; Zhu, L.
Chemical modification of stem bromelain with anhydride groups to enhance its stability and catalytic activity
J. Mol. Catal. B
63
188-193
2010
Ananas comosus
-
Ferreira, J.; Bresolin, L.; Silveira, E.; Tambourgi, E.
Purification of bromelain from ananas comosus by PEG/phosphate ATPS
Chem. Eng. Transact.
24
931-936
2011
Ananas comosus
-
Dave, S.; Mahajan, S.; Chandra, V.; Gupta, P.
Trifluoroethanol stabilizes the molten globule state and induces non-amyloidic turbidity in stem bromelain near its isoelectric point
Int. J. Biol. Macromol.
49
536-542
2011
Ananas comosus
Esti, M.; Benucci, I.; Liburdi, K.; Garzillo, A.M.
Effect of wine inhibitors on free pineapple stem bromelain activity in a model wine system
J. Agric. Food Chem.
59
3391-3397
2011
Ananas comosus
Amid, A.; Ismail, N.; Yusof, F.; Salleh, H.
Expression, purification, and characterization of a recombinant stem bromelain from Ananas comosus
Process Biochem.
46
2232-2239
2011
Ananas comosus
-
Ilaria, B.; Marco, E.; Katia, L.; Maria Vittoria, G.A.
Pineapple stem bromelain immobilized on different supports: catalytic properties in model wine
Biotechnol. Prog.
28
1472-1477
2012
Ananas comosus
Pavan, R.; Jain, S.; Shraddha, S.; Kumar, A.
Properties and therapeutic application of bromelain: a review
Biotechnol. Res. Int.
2012
976203
2012
Ananas comosus
Esti, M.; Benucci, I.; Liburdi, K.; Garzillo, A.
Immobilized pineapple stem bromelain activity in a wine-like medium: Effect of inhibitors
Food Bioprod. Process.
93
84-89
2015
Ananas comosus
-
Rani, A.; Venkatesu, P.
Insights into the interactions between enzyme and co-solvents: stability and activity of stem bromelain
Int. J. Biol. Macromol.
73
189-201
2015
Ananas comosus
Lopez-Garcia, B.; Hernandez, M.; Segundo, B.S.
Bromelain, a cysteine protease from pineapple (Ananas comosus) stem, is an inhibitor of fungal plant pathogens
Lett. Appl. Microbiol.
55
62-67
2012
Ananas comosus
George, S.; Bhasker, S.; Madhav, H.; Nair, A.; Chinnamma, M.
Functional characterization of recombinant bromelain of Ananas comosus expressed in a prokaryotic system
Mol. Biotechnol.
56
166-174
2014
Ananas comosus
Banks, J.M.; Herman, C.T.; Bailey, R.C.
Bromelain decreases neutrophil interactions with P-selectin, but not E-selectin, in vitro by proteolytic cleavage of P-selectin glycoprotein ligand-1
PLoS ONE
8
e78988
2013
Ananas comosus
Esti, M.; Benucci, I.; Lombardelli, C.; Liburdi, K.; Garzillo, A.
Papain from papaya (Carica papaya L.) fruit and latex: Preliminary characterization in alcoholic-acidic buffer for wine application
Food Bioprod. Process.
91
595-598
2013
Ananas comosus
Al-Otaibi, W.R.; Virk, P.; Elobeid, M.
Ameliorative potential of stem bromelain on lead-induced toxicity in Wistar rats
Acta Biol. Hung.
66
149-160
2015
Ananas comosus
Misran, E.; Idris, A.; Mat Sarip, S.; Yaakob, H.
Properties of bromelain extract from different parts of the pineapple variety Morris
Biocatal. Agricult. Biotechnol.
18
101095
2019
Ananas comosus
-
Manosroi, W.; Chankhampan, C.; Manosroi, J.; Manosroi, A.
In vitro anti-cancer activity comparison of the freeze-dried and spray-dried bromelain from pineapple stems
Chiang Mai J. Sci.
44
1407-1418
2017
Ananas comosus (P14518)
-
Ramli, A.N.M.; Manas, N.H.A.; Hamid, A.A.A.; Hamid, H.A.; Illias, R.M.
Comparative structural analysis of fruit and stem bromelain from Ananas comosus
Food Chem.
266
183-191
2018
Ananas comosus (P14518), Ananas comosus
Tap, F.; Majid, F.; Khairudin, N.
Structure prediction of stem bromelain from pineapples (Ananas comosus) using procaricain enzyme as a modelling template
Int. J. Appl. Eng. Res.
11
6109-6111
2016
Ananas comosus (F1KD58)
-
Bhakuni, K.; Venkatesu, P.
Does macromolecular crowding compatible with enzyme stem bromelain structure and stability?
Int. J. Biol. Macromol.
131
527-535
2019
Ananas comosus (P14518)
Sao Paulo Barretto Miranda, I.K.; Fontes Suzart Miranda, A.; Souza, F.V.; Vannier-Santos, M.A.; Pirovani, C.P.; Pepe, I.M.; Rodowanski, I.J.; Ferreira, K.T.; Mendes Souza Vaz, L.; de Assis, S.A.
The biochemical characterization, stabilization studies and the antiproliferative effect of bromelain against B16F10 murine melanoma cells
Int. J. Food Sci. Nutr.
68
442-454
2017
Ananas comosus (P14518), Ananas comosus, Ananas comosus AGB 772 (P14518)
Ghensi, P.; Cucchi, A.; Bonaccorso, A.; Ferroni, L.; Gardin, C.; Mortellaro, C.; Zavan, B.
In vitro effect of bromelain on the regenerative properties of mesenchymal stem cells
J. Craniofac. Surg.
30
1064-1067
2019
Ananas comosus (O24641), Ananas comosus
Kumar, P.; Jha, I.; Venkatesu, P.; Bahadur, I.; Ebenso, E.
A comparative study of the stability of stem bromelain based on the variation of anions of imidazolium-based ionic liquids
J. Mol. Liq.
246
178-186
2017
Ananas comosus (P14518)
-
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