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3.4.21.62: Subtilisin

This is an abbreviated version!
For detailed information about Subtilisin, go to the full flat file.

Word Map on EC 3.4.21.62

Reaction

Hydrolysis of proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. Hydrolyses peptide amides =

Synonyms

AcpII, Ak.1 protease, Alcalase, Alcalase 0.6L, Alcalase 2.5L, ALE1 subtilase, ALK-enzyme, Alkaline mesentericopeptidase, Alkaline protease, alkaline serine protease, ALP1, Alzwiprase, aprE, AprE51, aqualysin, Arp, AsES, Asp v 13, AtSBT1.9, Bacillopeptidase A, Bacillopeptidase B, Bacillus gibsonii alkaline protease, Bacillus subtilis alkaline proteinase Bioprase, BgAP, Bioprase AL 15, Bioprase APL 30, BLS, BPN', BprB, BprV, C1 subtilase, cold active subtilisin-like serine proteinase, Colistinase, EC 3.4.21.14, EC 3.4.4.16, Esperase, Fe protease, Fe prtS8A, Genenase I, intracellular subtilisin protease, ISP, IvaP, Kazusase, Maxatase, mesenteroicopeptidase, More, Nagarse, Opticlean, ORF2, Orientase 10B, P69 subtilase, PBANKA_1106900, PbSOPT, Peptidase, subtilo-, A, PF3D7_0507300, phytophase, PIMMS2, Protease S, Protease VIII, Protease XXVII, Proteinase K, Proteinase, Bacillus subtilis alkaline, Protin A 3L, PSP-3, psychrophilic subtilisin-like protease, S1P subtilase, SAP, SAS-1, SASP, saspase, Savinase, Savinase 16.0L, Savinase 32.0 L EX, Savinase 4.0T, Savinase 8.0L, savinaseTM, SBc, SBL, SDD1 subtilase, senescence-associated subtilisin protease, SES7, SISBT3 subtilase, SOPT, SP 266, Sspa, SSU0757, SUB1, SUB2, subC, subtilase, subtilase subfamily 1 member 9, subtilase-like protease, subtilisin, subtilisin 72, subtilisin A, Subtilisin amylosacchariticus, Subtilisin BL, subtilisin BPN’, subtilisin C., subtilisin Carlsberg, subtilisin DJ-4, Subtilisin DY, Subtilisin E, subtilisin E-S7, Subtilisin GX, subtilisin JB1, subtilisin Karlsberg, Subtilisin Novo, subtilisin Pr1-like protease, subtilisin protease, subtilisin QK, Subtilisin S41, subtilisin S4I, subtilisin S88, Subtilisin Sendai, subtilisin Sph, subtilisin-like ookinete protein, subtilisin-like ookinete protein important for transmission, subtilisin-like protease, subtilisin-like protease AprV2, subtilisin-like serine protease, Subtilisn J, Subtilopeptidase, Superase, thermitase, thermo-active subtilisin-like serine protease, Thermoase, Thermoase PC 10, thermophilic thermitase, thermostable subtilisin, ThSS45, Tk-subtilisin, trans-cinnamoyl-subtilisin, V. cholerae-secreted serine protease, VC_0157, vPR

ECTree

     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.62 Subtilisin

Inhibitors

Inhibitors on EC 3.4.21.62 - Subtilisin

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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(dimethylamino)-1-naphthalenesulfonyl fluoride
-
100% inhibition of enzyme activity with N-trans cinnamoyl imidazole as substrate, during prolonged exposure to organic solvents the active-site fluorescent label inhibitor adopts a different binding conformation
1,10-phenanthroline
at 37°C and pH of 7.5, 0.1 mM inhibits prosubtilisin JB1 by 40%
1,4-dioxane
2,2'-[[(1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphoryl]bis(oxybenzene-4,1-diyl)]diacetic acid
-
-
2,2'-[[(1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphoryl]bis(oxybenzene-4,1-diyl)]diacetic acid
-
-
2,2'-[[(1-[[1-(tert-butoxycarbonyl)-L-prolyl]amino]-3-methylbutyl)phosphoryl]bis(oxybenzene-3,1-diyl)]diacetic acid
-
-
2-phenylethaneboronic acid
-
-
2-phenylethanesulfonic acid
-
-
3,4-dichloroisocoumarin
-
-
4-(2-aminoethyl)-benzenesulfonyl fluoride
-
-
4-(2-aminoethyl)benzenesulfonyl fluoride
-
-
4-(4'-Aminophenylazo)phenylarsonic acid
-
-
4-bromophenacyl bromide
-
-
5-Dimethylaminonaphthalene-1-sulfonate
-
circular-dichroism and fluorescence studies of 5-dimethylaminonaphthalene-1-sulfonyl derivative of subtilisin indicate a closely similar structure to that of native subtilisin
acetonitril
high concentrations of acetonitrile significantly decrease the enzyme activity by over 60%, most likely due to disrupting the enzyme structural integrity
alpha2-Macroglobulin
-
inhibits alkaline proteolytic activity of purified Arp by 80%
-
angiotensin-converting enzyme
-
IC50 is 0.067 mg/ml
-
antipain
Aprotinin
benzeneboronic acid
-
-
Benzenesulfonic acid
-
-
Benzyloxycarbonyl-(Ala)n-PheCH2Cl
-
benzyloxycarbonyl-(Ala)2-PheCH2Cl is the best inhibitor
Benzyloxycarbonyl-Ala-XaaCH2Cl
-
Xaa : Gly, Val, Ala, Leu, Phe
Benzyloxycarbonyl-L-phenylalanylbromomethane
-
reactivity is about an order of magnitude less than that of subtilisins BPN' and Carlsberg
bis(2,3,5-trimethylphenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(2,3-dimethylphenyl) (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis(2,3-dimethylphenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(2,5-dimethylphenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(2-methylphenyl) (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis(2-methylphenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(3,4,5-trimethylphenyl) (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis(3,4,5-trimethylphenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(3,4-dimethylphenyl) (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis(3,4-dimethylphenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(3-chlorophenyl) (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis(3-chlorophenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(3-methoxyphenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(4-chlorophenyl) (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis(4-chlorophenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(4-ethylphenyl) (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis(4-ethylphenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(4-methoxyphenyl) (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis(4-methylphenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis(4-tert-butylphenyl) (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis(4-tert-butylphenyl) (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis[4-(methylsulfonyl)phenyl] (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis[4-(propan-2-yl)phenyl] (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis[4-(propan-2-yl)phenyl] (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
bis[4-(sulfanylmethyl)phenyl] (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
bis[4-(sulfanylmethyl)phenyl] (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
Brij 35
at 37°C and pH of 7.5, 0.01% reduces prosubtilisin JB1 relative activity to 30% and 0.05% reduces prosubtilisin JB1 relative activity to 70%
Broad bean extract
-
subtilisin BPN'
Ca2+
at 37°C and pH of 7.5, 1 mM reduces prosubtilisin JB1 relative activity to 57% and 5 mM reduces prosubtilisin JB1 relative activity to 45%
Chiral amine- and aminoalcohol-derivatives
-
-
-
chymostatin
Chymotrypsin I inhibitor from potato
-
subtilisin Carlsberg, subtilisin BPN'
-
chymotrypsin inhibitor 2
-
-
-
chymotrypsin inhibitor 2 mutant M59A
-
-
-
chymotrypsin inhibitor 2 mutant M59F
-
-
-
chymotrypsin inhibitor 2 mutant M59G
-
-
-
chymotrypsin inhibitor 2 mutant M59K
-
-
-
chymotrypsin inhibitor 2 mutant M59Y
-
-
-
chymotrypsin inhibitor 2 mutant Y61A
-
-
-
Co2+
at 37°C and pH of 7.5, 1 mM reduces prosubtilisin JB1 relative activity to 14% and 5 mM reduces prosubtilisin JB1 relative activity to 24%
CrSPI-1
-
Kazal-type inhibitor from the hepatopancreas of the Carcinoscorpius rotundicauda, potently inhibits subtilisin
-
diisopropyl fluorophosphate
-
-
diisopropylphosphofluoridate
-
-
Dipeptidyl chloromethyl ketones
-
-
diphenyl (1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)phosphonate
-
-
diphenyl (1-[[(benzyloxy)carbonyl]amino]-3-methylbutyl)phosphonate
-
-
duck ovomucoid
-
-
-
E-64c
at 37°C and pH of 7.5, 0.1 mM inhibits prosubtilisin JB1 by 25%
EGTA
at 37°C and pH of 7.5, 0.1 mM inhibits prosubtilisin JB1 by 34%
Elastatinol
-
weak
EPI1a
-
four-cysteine atypical Kazal-domain of protease inhibitor EPI1 from Phytophthora infestans. 80% inhibition at 0.00015 mM
-
EPI1b
-
typical Kazal-domain of protease inhibitor EPI1 from Phytophthora infestans, little inhibitory effect
-
fungal protease inhibitor F
-
specific inhibitor toward subtilisin-type protease. P1 residue most signficantly affects inhibitory specificity. Mutant T29M has stronger subtilisin-inhibitory activity than the wild-type, mutants T29E and T29R are relatively weaker inhibitors. Inhibitory activities of mutants T29F and T29L are as strong as that of the wild-type
-
guanidine hydrochloride
-
at 2 M inhibits subtilisin-like serine protease by 35% and at 4 M almost completely, whereas it has no inhibitory effect on subtilisin
guanidinium hydrochloride
-
H2O2
-
the enzyme activity is reduced to 68% after a 20-min incubation with 0.33% hydrogen peroxide at 25°C in Tris buffer, substrate suc-Ala-Ala-Pro-Phe-4-nitroanilide, recombinant enzyme
Hg+
at 37°C and pH of 7.5, 1 mM reduces prosubtilisin JB1 relative activity to 33% and 5 mM reduces prosubtilisin JB1 relative activity to 22%
human LEKTI
-
noncompetitive inhibition
-
human proteinase inhibitor 9
-
PI9, serine proteinase inhibitor
-
Hydrocinnamamide
-
-
Hydrocinnamate
-
-
Inhibitor from Dolichos biflorus
-
purification and properties
-
Inhibitor from egg white
-
Inhibitor from seeds of Canavalia lineata
-
Inhibitor from seeds of Setaria italica
-
purification and characterization
-
Inhibitor from Streptomyces sp.
-
-
-
Inhibitor from Streptomyces virginiae
-
primary structure
-
Inhibitor from Vigna unguiculata subsp. cylindrica
-
Inhibitor of Amaranthus caudatus seeds
-
Inhibitor of trypsin from soybean
-
-
-
iodoacetamide
-
-
IvaP I9 domain
the N-terminal propeptide of enzyme IvaP, the IvaP I9 domain, can temporarily inhibit, and be cleaved by, the purified enzyme
-
K+
at 37°C and pH of 7.5, with 1 mM results in an almost complete reduction of prosubtilisin JB1 activity, 5 mM reduces prosubtilisin JB1 relative activity to 53%
L-[(1R)-1-acetamido-2-(1-naphthyl)ethyl]boronic acid
-
leupeptin
-
inhibits the enzymatic activity by 20%
Methaneboronic acid
-
-
Mg2+
at 37°C and pH of 7.5, 1 mM reduces prosubtilisin JB1 relative activity to 79% and 5 mM reduces prosubtilisin JB1 relative activity to 48%
N-((tert-Butoxycarbonyl)alanylprolylphenylalanyl)-O-benzoylhydroxylamine
-
-
N-(tert-butoxycarbonyl)-L-valyl-N-(1-[bis[4-(sulfanylmethyl)phenoxy]phosphoryl]-2-phenylethyl)-L-prolinamide
-
-
N-(tert-butoxycarbonyl)-L-valyl-N-[1-(diphenoxyphosphoryl)-2-phenylethyl]-L-prolinamide
-
-
N-(tert-butoxycarbonyl)-L-valyl-N-[1-[bis(3,4,5-trimethylphenoxy)phosphoryl]-3-methylbutyl]-L-prolinamide
-
-
N-(tert-butoxycarbonyl)-L-valyl-N-[1-[bis(4-methoxyphenoxy)phosphoryl]-3-methylbutyl]-L-prolinamide
-
-
N-(tert-butoxycarbonyl)-L-valyl-N-[1-[bis(4-tert-butylphenoxy)phosphoryl]-3-methylbutyl]-L-prolinamide
-
-
N-acetyl-L-tryptophan amide
molecular dynamics simulations are performed with subtilisin in the presence and in the absence of an inhibitor both in hexane and in water. The inhibitor induces an open conformation of the S1 pocket that is maintained after the removal of the ligand in anhydrous, but not in aqueous, simulations. The analysis of fluctuations suggest that this behavior is caused by the decreased flexibility exhibited by subtilisin in hexane
N-benzoyl-L-Arg
-
product inhibition
N-benzyloxycarbonyl-Ala-Pro-Phe-chloromethyl ketone
-
synthetic inhibitor
N-ethylmaleimide
at 37°C and pH of 7.5, 0.1 mM inhibits prosubtilisin JB1 by 15%
N-tosyl-L-phenylalanyl chloromethyl ketone
-
-
N1-18[ISP]
synthetic peptide corresponding to the N-terminal extension behaves as a mixed noncompetitive inhibitor of active ISP
neurolysin
-
IC50 is 0.263 mg/ml
-
nitrogen
p-chloromercuribenzoate
-
partial inhibition
p-Nitrophenylarsonate
-
-
p-Tolylarsonate
-
-
pepstatin
-
almost completely inhibits acid proteolytic activity, does not inhibit alkaline proteolytic activity of purified Arp
pepstatin A
at 37°C and pH of 7.5, 0.1 mM inhibits prosubtilisin JB1 by 48%
Peptidyl chloromethyl ketones
-
-
phenylmethanesulfonyl fluoride
phenylmethylsulfonyl fluoride
Phenylmethylsulphonyl fluoride
-
-
Potato extract
-
subtilisin BPN'
-
propeptide
-
inhibition in a concentration-dependent manner. Wild-type propeptide is more potent than G56W-, G56S- and G56E-propeptide
-
Sodium dodecyl sulfate
Suc-Val-Pro-PheP(OPh)2
-
-
sucrose
tert-butyl (2S)-2-([1-[bis(2-methylphenoxy)phosphoryl]-3-methylbutyl]carbamoyl)pyrrolidine-1-carboxylate
-
-
tert-butyl (2S)-2-([1-[bis(3,4,5-trimethylphenoxy)phosphoryl]-3-methylbutyl]carbamoyl)pyrrolidine-1-carboxylate
-
-
tert-butyl (2S)-2-([1-[bis(3,4-dimethylphenoxy)phosphoryl]-3-methylbutyl]carbamoyl)pyrrolidine-1-carboxylate
-
-
tert-butyl (2S)-2-([1-[bis(4-methoxyphenoxy)phosphoryl]-3-methylbutyl]carbamoyl)pyrrolidine-1-carboxylate
-
-
tert-butyl (2S)-2-([1-[bis(4-methylphenoxy)phosphoryl]-3-methylbutyl]carbamoyl)pyrrolidine-1-carboxylate
-
-
tert-butyl (2S)-2-[(1-[bis[4-(sulfanylmethyl)phenoxy]phosphoryl]-2-phenylethyl)carbamoyl]pyrrolidine-1-carboxylate
-
-
tert-butyl (2S)-2-[[1-(diphenoxyphosphoryl)-2-phenylethyl]carbamoyl]pyrrolidine-1-carboxylate
-
-
tomato inhibitor-II
-
TI-II, enzyme binding structure, the interdomain interface in TI-II consists of a small cluster of highly conserved hydrophobic residues Ile14, Pro16, Tyr98, Phe100 and Phe106 from domain I and Tyr34, Pro54 and Lys55 from domain II. Although this interface is quite small (buried surface area of 487A), it forms a stable packing arrangement between the two domains. Each reactive site loop in TI-II interacts with a separate molecule of subtilisin in the canonical manner observed in other proteinase–inhibitor complexes. The domains of TI-II appear to bind the proteinase independently of each other
-
tosyl-Phe chloromethyl ketone
Triton X-100
at 37°C and pH of 7.5, 0.01% reduces prosubtilisin JB1 relative activity to 92% and 0.05% reduces prosubtilisin JB1 relative activity to 69%
turkey egg white inhibitor
-
Tween 20
at 37°C and pH of 7.5, 0.01% reduces prosubtilisin JB1 relative activity to 53% and 0.05% reduces prosubtilisin JB1 relative activity to 70%
Urea
high concentrations (6 M) of urea significantly decrease the enzyme activity by over 60%, most likely due to disrupting the enzyme structural integrity
additional information
-