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Information on EC 4.6.1.18 - pancreatic ribonuclease and Organism(s) Lithobates pipiens and UniProt Accession P22069
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4.6.1.18 pancreatic ribonucleaseIUBMB Comments
Specifically cleaves at the 3'-side of pyrimidine (uracil or cytosine) phosphate bonds in RNA. The reaction takes place in two steps, with the 2',3'-cyclic phosphodiester intermediates released from the enzyme at the completion of the first step. Hydrolysis of these cyclic compounds occurs at a much slower rate through a reversal of the first step, in which the -OH group of water substitutes for the 2'-OH group of the ribose used in the first step, and does not take place until essentially all the susceptible 3',5'-phosphodiester bonds have been cyclised. The enzyme can act as an endo- or exo ribonuclease.
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Word Map
- 4.6.1.18
- asthma
-
allergic
- airway
-
asthmatic
- bronchial
- ige
-
atopic
- pollen
- nasal
- granule
- rhinitis
- sputum
- lavage
-
inhale
-
self-incompatibility
-
expiratory
- eosinophilia
-
degranulation
- histamine
- myeloperoxidase
- tryptase
-
mast
-
leukotriene
-
hyperresponsiveness
-
angiogenin
-
provocation
- methacholine
- pistil
- gametophytic
-
prick
- solanaceae
- rosaceae
-
spirometry
-
nonatopic
-
wheezing
-
ribonucleolytic
-
exhaled
-
fluticasone
- dermatophagoides
-
aeroallergens
-
budesonide
-
nonallergic
-
allergen-induced
- eotaxin
-
interleukin-5
- synthesis
- agriculture
-
hypereosinophilic
- diagnostics
- medicine
-
beclomethasone
-
beta2-agonists
- analysis
- drug development
- pharmacology
-
sil-2r
- s-protein
- biotechnology
The taxonomic range for the selected organisms is: Lithobates pipiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
hide(Overall reactions are displayed. Show all >>)
+
=
+
an [RNA] containing cytidine
+
=
an [RNA]-3'-cytidine-3'-phosphate
+
a 5'-hydroxy-ribonucleotide-3'-[RNA]
+
=
+
an [RNA] containing uridine
+
=
an [RNA]-3'-uridine-3'-phosphate
+
a 5'-hydroxy-ribonucleotide-3'-[RNA]
Synonyms
eosinophil cationic protein, s-rnase, pancreatic ribonuclease, onconase, eosinophil-derived neurotoxin, pancreatic rnase, bovine pancreatic ribonuclease a, bs-rnase, rnase 1, rnase1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alkaline ribonuclease
-
-
-
-
Ceratitis capitata alkaline ribonuclease
-
-
-
-
Eosinophil-derived neurotoxin
-
-
-
-
gene S glycoproteins
-
-
-
-
gene S locus-specific glycoproteins
-
-
-
-
glycoproteins, gene S locus-specific
-
-
-
-
glycoproteins, S-genotype-asssocd
-
-
-
-
glycoproteins, SLSG
-
-
-
-
glycoproteins, specific or class, gene S
-
-
-
-
glycoproteins, specific or class, SLSG (gene S locus-specific glycoprotein)
-
-
-
-
nuclease, ribo-
-
-
-
-
pancreatic RNase
-
-
-
-
ribonuclease
-
-
-
-
ribonuclease A
-
-
-
-
ribonuclease I
-
-
-
-
Ribonuclease US
-
-
-
-
ribonuclease W1
-
-
-
-
ribonucleate 3'-pyrimidino-oligonucleotidohydrolase
-
-
-
-
ribonucleic phosphatase
-
-
-
-
RL1
-
-
-
-
RNase
-
-
-
-
RNase A
-
-
-
-
RNase I
-
-
-
-
S-RNase
-
-
-
-
Seminal RNase
-
-
-
-
SLSG glycoproteins
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
an [RNA] containing cytidine + H2O = an [RNA]-3'-cytidine-3'-phosphate + a 5'-hydroxy-ribonucleotide-3'-[RNA]
RNase A catalyzes a well-characterized acid-base mechanism involving two histidines (His12 and His119) and a transition state stabilizing positive charge (Lys41). The transphosphorylation of a single-stranded RNA molecule by the enzyme yields a 2',3'-cyclic phosphomonoester intermediate, which can be expelled from the active site or hydrolyzed in a microscopic reverse reaction involving the same two histidines
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
RNA lyase ([RNA]-3'-cytidine/uridine-3'-phosphate and 5'-hydroxy-ribonucleotide-3'-[RNA] producing)
Specifically cleaves at the 3'-side of pyrimidine (uracil or cytosine) phosphate bonds in RNA. The reaction takes place in two steps, with the 2',3'-cyclic phosphodiester intermediates released from the enzyme at the completion of the first step. Hydrolysis of these cyclic compounds occurs at a much slower rate through a reversal of the first step, in which the -OH group of water substitutes for the 2'-OH group of the ribose used in the first step, and does not take place until essentially all the susceptible 3',5'-phosphodiester bonds have been cyclised. The enzyme can act as an endo- or exo ribonuclease.
CAS REGISTRY NUMBER
COMMENTARY
9001-99-4
-
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
6-carboxyfluorescein-dArUdAdA-6-carboxytetramethylrhodamine + H2O
?
-
-
-
?
6-carboxyfluorescein-dArUdGdA-6-carboxytetramethylrhodamine + H2O
?
-
-
-
?
18S rRNA + H2O
3'-phosphomononucleotides + 3'-phosphooligonucleotides
-
-
-
-
?
28S rRNA + H2O
3'-phosphomononucleotides + 3'-phosphooligonucleotides
-
-
-
-
?
RNA + H2O
3'-phosphomononucleotides + 3'-phosphooligonucleotides
-
endonucleolytic cleavage to 3'-phosphomononucleotides and 3'-phosphooligonucleotides ending in Cp or Up with 2',3'-cyclic phosphate intermediates, e.g. tRNA, 18S and 28S rRNA, yeast RNA,4.5S RNA
-
-
?
tRNA + H2O
3'-phosphomononucleotides + 3'-phosphooligonucleotides
-
onconase, similar enzyme
-
-
?
tRNAlys + H2O
3'-phosphomononucleotides + 3'-phosphooligonucleotides
-
-
-
-
?
tRNAMet + H2O
3'-phosphomononucleotides + 3'-phosphooligonucleotides
-
-
-
-
?
tRNAPhe + H2O
3'-phosphomononucleotides + 3'-phosphooligonucleotides
-
-
-
-
?
tRNAVal + H2O
3'-phosphomononucleotides + 3'-phosphooligonucleotides
-
-
-
-
?
additional information
?
-
the enzyme degrades single-stranded and/or double-stranded RNA
-
-
?
additional information
?
-
-
enzyme expressed in K-562 cell is cytotoxic and cytostatic, IC50 value 0.0009 mM
-
-
?
additional information
?
-
-
predominant cleavage sites for onconase are at UG and GG residues. With the tRNA substrates studied, the predominant cleavages mapin the triplet UGG located in the context of the variable loop or the D-arm of the tRNA
-
-
?
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
RNA + H2O
3'-phosphomononucleotides + 3'-phosphooligonucleotides
-
endonucleolytic cleavage to 3'-phosphomononucleotides and 3'-phosphooligonucleotides ending in Cp or Up with 2',3'-cyclic phosphate intermediates, e.g. tRNA, 18S and 28S rRNA, yeast RNA,4.5S RNA
-
-
?
additional information
?
-
the enzyme degrades single-stranded and/or double-stranded RNA
-
-
?
additional information
?
-
-
enzyme expressed in K-562 cell is cytotoxic and cytostatic, IC50 value 0.0009 mM
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme belongs to the vertebrate pancreatic-like RNase A superfamily, sequence comparisons and phylogenetic analysis, overview
additional information
RNA subsites and reaction mechanism catalyzed by RNase A, molecular interactions between the RNA substrate and residues of the catalytic groove. The following residues are known to interact with each subsite: Lys66 (P0), Thr45 and Asp83 (B1), Gln11, His12, Lys41, His119, and Asp121 (P1), Asn71 and Glu111 (B2), and Lys7 and Arg10 (P2). Structure-function relationship, overview. Potential role for catalytic base His119 in ligand discrimination and/or stabilization in addition to its critical role in catalysis, molecular dynamic simulations show that His119 adopts both rotameric positions in solution, most likely experiencing conformational exchange over the course of a catalytic reaction. Functional importance of long-range conformational rearrangements in RNase A
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). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
comparison of folding kinetics with bovine RNase A and angiogenin at pH 8.0 and 15°C. Direct correlation between the number of cis-prolyl bonds in a native protein and the complexity with which it folds via slower phases
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
wild-type in complex with oligonucleotide d(AUGA) at 1.9 A resolution, mutant T89N/E91A in complex with 5'-AMP at 1.65 A resolution. In wild-type, residue E91 forms two hydrogen bonds with the guanine nucleobase in d(AUGA), and T89 is in close proximity to that nucleobase. One nucleic acid molecule is bound to one enzyme molecule. In the mutant, four 5'-AMP molecules are bound to each enzyme molecule in a non-productive mode
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C87A/C104A
66% of wild-type activity, decrease in melting temperature
T89N/E91A
mutant prefers adenine over guanine 2.6fold, crystallization data of mutant in complex with 5'-AMP
C87A/C104A
-
66% of wild-type activity, reduced cytotoxic and cytostatic properties, IC50 values for K-562 cells 0.0046 mM
F28A
-
61% of wild-type activity, reduced cytotoxic and cytostatic properties, IC50 values for K-562 cells 0.0043 mM
F28T
-
60% of wild-type activity, reduced cytotoxic and cytostatic properties, IC50 values for K-562 cells 0.0037 mM
F36A
-
69% of wild-type activity, reduced cytotoxic and cytostatic properties, IC50 values for K-562 cells 0.0039 mM
F36Y
-
80% of wild-type activity, reduced cytotoxic and cytostatic properties, IC50 values for K-562 cells 0.0027 mM
Glp1E
-
41% of wild-type activity, reduced cytotoxic and cytostatic properties, IC50 values for K-562 cells 0.0099 mM
glp1P
-
44% of wild-type activity, reduced cytotoxic and cytostatic properties, IC50 values for K-562 cells 0.015 mM
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the extremely high thermodynamic stability of enzyme is due to a dramatic deceleration of the unfolding reaction
additional information
-
the extremely high thermodynamic stability of enzyme is due to a dramatic deceleration of the unfolding reaction
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
comparison of folding kinetics with bovine RNase A and angiogenin at pH 8.0 and 15°C. Direct correlation between the number of cis-prolyl bonds in a native protein and the complexity with which it folds via slower phases
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boix, E.; Wu, Y.; Vasandani, V.M.; Saxena, S.K.; Ardelt, W.; Ladner, J.; Youle, R.J.
Role of the N terminus in RNase A homologues: differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity
J. Mol. Biol.
257
992-1007
1996
Bos taurus, Homo sapiens, Lithobates pipiens
Arnold, U.; Schulenburg, C.; Schmidt, D.; Ulbrich-Hofmann, R.
Contribution of structural peculiarities of onconase to its high stability and folding kinetics
Biochemistry
45
3580-3587
2006
Lithobates pipiens (P22069), Lithobates pipiens
Schulenburg, C.; Ardelt, B.; Ardelt, W.; Arnold, U.; Shogen, K.; Ulbrich-Hofmann, R.; Darzynkiewicz, Z.
The interdependence between catalytic activity, conformational stability, and cytotoxicity of onconase
Cancer Biol. Ther.
6
1233-1239
2007
Lithobates pipiens
Pradeep, L.; Shin, H.C.; Scheraga, H.A.
Correlation of folding kinetics with the number and isomerization states of prolines in three homologous proteins of the RNase family
FEBS Lett.
580
5029-5032
2006
Bos taurus, Lithobates pipiens
Suhasini, A.N.; Sirdeshmukh, R.
Transfer RNA cleavages by onconase reveal unusual cleavage sites
J. Biol. Chem.
281
12201-12209
2006
Lithobates pipiens
Lee, J.E.; Bae, E.; Bingman, C.A.; Phillips, G.N.; Raines, R.T.
Structural basis for catalysis by onconase
J. Mol. Biol.
375
165-177
2008
Lithobates pipiens (P22069), Lithobates pipiens
Torrent, G.; Ribo, M.; Benito, A.; Vilanova, M.
Bactericidal activity engineered on human pancreatic ribonuclease and onconase
Mol. Pharm.
6
531-542
2009
Homo sapiens, Lithobates pipiens
Gagne, D.; Doucet, N.
Structural and functional importance of local and global conformational fluctuations in the RNase A superfamily
FEBS J.
280
5596-5607
2013
Gallus gallus, Homo sapiens, Danio rerio (A5HAK0), Bos taurus (P00669), Rattus norvegicus (P00684), Lithobates pipiens (P22069)
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