| Pancreatic ribonuclease |
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Structure of RNase A
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| Identifiers |
| EC number |
3.1.27.5 |
| CAS number |
9001-99-4 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
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| Pancreatic ribonuclease |
| Identifiers |
| Symbol |
RNaseA |
| Pfam |
PF00074 |
| InterPro |
IPR001427 |
| SMART |
SM00092 |
| PROSITE |
PDOC00118 |
| Available protein structures: |
| Pfam |
structures |
| PDB |
RCSB PDB; PDBe; PDBj |
| PDBsum |
structure summary |
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Pancreatic ribonucleases (EC 3.1.27.5, RNase, RNase I, RNase A, pancreatic RNase, ribonuclease I, endoribonuclease I, ribonucleic phosphatase, alkaline ribonuclease, ribonuclease, gene S glycoproteins, Ceratitis capitata alkaline ribonuclease, SLSG glycoproteins, gene S locus-specific glycoproteins, S-genotype-assocd. glycoproteins, ribonucleate 3'-pyrimidino-oligonucleotidohydrolase) are pyrimidine-specific endonucleases found in high quantity in the pancreas of certain mammals and of some reptiles.[1]
Specifically, the enzymes are involved in endonucleolytic cleavage of 3'-phosphomononucleotides and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates. Ribonuclease can unwind the RNA helix by complexing with single-stranded RNA; the complex arises by an extended multi-site cation-anion interaction between lysine and arginine residues of the enzyme and phosphate groups of the nucleotides.
Contents
- 1 Notable family members
- 2 Human genes
- 3 Cytotoxicity
- 4 References
Notable family members
Bovine pancreatic ribonuclease is the best-studied member of the family and has served as a model system in work related to protein folding, disulfide bond formation, protein crystallography and spectroscopy, and protein dynamics.[2]
Other proteins belonging to the pancreatic ribonuclease superfamily include: bovine seminal vesicle and brain ribonucleases; kidney non-secretory ribonucleases;[3] liver-type ribonucleases;[4] angiogenin, which induces vascularisation of normal and malignant tissues; eosinophil cationic protein,[5] a cytotoxin and helminthotoxin with ribonuclease activity; and frog liver ribonuclease and frog sialic acid-binding lectin. The sequence of pancreatic ribonucleases contains four conserved disulfide bonds and three amino acid residues involved in the catalytic activity.[6]
Human genes
Human genes encoding proteins containing this domain include:
- ANG,
- RNASE1, RNASE10, RNASE12, RNASE2, RNASE3, RNASE4, RNASE6, RNASE7, and RNASE8.
Cytotoxicity
Some members of the pancreatic ribonuclease family have cytotoxic effects. Mammalian cells are protected from these effects due to their extremely high affinity for ribonuclease inhibitor (RI), which protects cellular RNA from degradation by pancreatic ribonucleases.[7] Pancreatic ribonucleases that are not inhibited by RI are approximately as toxic as alpha-sarcin, diphtheria toxin, or ricin.[8]
Two pancreatic ribonucleases isolated from the oocytes of the Northern leopard frog - amphinase and ranpirnase - are not inhibited by RI and show differential cytotoxicity against tumor cells.[9] Ranpirnase was studied in a Phase III clinical trial as a treatment candidate for mesothelioma, but the trial did not demonstrate statistical significance against primary endpoints.[10]
References
- ^ Beintema JJ, van der Laan JM (1986). "Comparison of the structure of turtle pancreatic ribonuclease with those of mammalian ribonucleases". FEBS Lett. 194 (2): 338–343. doi:10.1016/0014-5793(86)80113-2. PMID 3940901.
- ^ Marshall GR, Feng JA, Kuster DJ (2008). "Back to the future: ribonuclease A". Biopolymers. 90 (3): 259–77. doi:10.1002/bip.20845. PMID 17868092.
- ^ Rosenberg HF, Tenen DG, Ackerman SJ (1989). "Molecular cloning of the human eosinophil-derived neurotoxin: a member of the ribonuclease gene family". Proc. Natl. Acad. Sci. U.S.A. 86 (12): 4460–4464. doi:10.1073/pnas.86.12.4460. PMC 287289. PMID 2734298.
- ^ Hofsteenge J, Matthies R, Stone SR (1989). "Primary structure of a ribonuclease from porcine liver, a new member of the ribonuclease superfamily". Biochemistry. 28 (25): 9806–9813. doi:10.1021/bi00451a040. PMID 2611266.
- ^ Rosenberg HF, Ackerman SJ, Tenen DG (1989). "Human eosinophil cationic protein. Molecular cloning of a cytotoxin and helminthotoxin with ribonuclease activity". J. Exp. Med. 170 (1): 163–176. doi:10.1084/jem.170.1.163. PMC 2189377. PMID 2473157.
- ^ Raines RT (1998). "Ribonuclease A". Chem. Rev. 98 (3): 1045–1066. doi:10.1021/cr960427h. PMID 11848924.
- ^ Gaur, D; Swaminathan, S; Batra, JK (6 July 2001). "Interaction of human pancreatic ribonuclease with human ribonuclease inhibitor. Generation of inhibitor-resistant cytotoxic variants.". The Journal of Biological Chemistry. 276 (27): 24978–84. doi:10.1074/jbc.m102440200. PMID 11342552.
- ^ Saxena, SK; Rybak, SM; Winkler, G; Meade, HM; McGray, P; Youle, RJ; Ackerman, EJ (5 November 1991). "Comparison of RNases and toxins upon injection into Xenopus oocytes.". The Journal of Biological Chemistry. 266 (31): 21208–14. PMID 1939163.
- ^ Lee JE, Raines RT (2008). "Ribonucleases as novel chemotherapeutics : the ranpirnase example". BioDrugs. 22 (1): 53–58. doi:10.2165/00063030-200822010-00006. PMC 2802594. PMID 18215091.
- ^ "Alfacell Annual Report 2009" (PDF). Retrieved 2 February 2015.
This article incorporates text from the public domain Pfam and InterPro IPR001427
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Hydrolase: esterases (EC 3.1)
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3.1.1: Carboxylic
ester hydrolases |
- Cholinesterase
- Acetylcholinesterase
- Butyrylcholinesterase
- Pectinesterase
- 6-phosphogluconolactonase
- PAF acetylhydrolase
- Lipase
- Bile salt-dependent
- Gastric/Lingual
- Pancreatic
- Lysosomal
- Hormone-sensitive
- Endothelial
- Hepatic
- Lipoprotein
- Monoacylglycerol
- Diacylglycerol
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| 3.1.2: Thioesterase |
- Palmitoyl protein thioesterase
- Ubiquitin carboxy-terminal hydrolase L1
- 4-hydroxybenzoyl-CoA thioesterase
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| 3.1.3: Phosphatase |
- Alkaline phosphatase
- Acid phosphatase (Prostatic)/Tartrate-resistant acid phosphatase/Purple acid phosphatases
- Nucleotidase
- Glucose 6-phosphatase
- Fructose 1,6-bisphosphatase
- Protein phosphatase
- OCRL
- Pyruvate dehydrogenase phosphatase
- Fructose 6-P,2-kinase:fructose 2,6-bisphosphatase
- PTEN
- Phytase
- Inositol-phosphate phosphatase
- Protein phosphatase: Protein tyrosine phosphatase
- Protein serine/threonine phosphatase
- Dual-specificity phosphatase
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| 3.1.4: Phosphodiesterase |
- Autotaxin
- Phospholipase
- Sphingomyelin phosphodiesterase
- PDE1
- PDE2
- PDE3
- PDE4A/PDE4B
- PDE5
- Lecithinase (Clostridium perfringens alpha toxin)
- Cyclic nucleotide phosphodiesterase
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| 3.1.6: Sulfatase |
- arylsulfatase
- Arylsulfatase A
- Arylsulfatase B
- Arylsulfatase E
- Steroid sulfatase
- Galactosamine-6 sulfatase
- Iduronate-2-sulfatase
- N-acetylglucosamine-6-sulfatase
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Nuclease (includes
deoxyribonuclease and
ribonuclease) |
| 3.1.11-16: Exonuclease |
| Exodeoxyribonuclease |
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| Exoribonuclease |
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| 3.1.21-31: Endonuclease |
| Endodeoxyribonuclease |
- Deoxyribonuclease I
- Deoxyribonuclease II
- Deoxyribonuclease IV
- Restriction enzyme
- UvrABC endonuclease
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| Endoribonuclease |
- RNase III
- RNase H
- RNase P
- RNase A
- RNase T1
- RNA-induced silencing complex
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| either deoxy- or ribo- |
- Aspergillus nuclease S1
- Micrococcal nuclease
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Enzymes
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| Activity |
- Active site
- Binding site
- Catalytic triad
- Oxyanion hole
- Enzyme promiscuity
- Catalytically perfect enzyme
- Coenzyme
- Cofactor
- Enzyme catalysis
- Enzyme kinetics
- Lineweaver–Burk plot
- Michaelis–Menten kinetics
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| Regulation |
- Allosteric regulation
- Cooperativity
- Enzyme inhibitor
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| Classification |
- EC number
- Enzyme superfamily
- Enzyme family
- List of enzymes
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| Types |
- EC1 Oxidoreductases(list)
- EC2 Transferases(list)
- EC3 Hydrolases(list)
- EC4 Lyases(list)
- EC5 Isomerases(list)
- EC6 Ligases(list)
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