Pancreatic ribonuclease family

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Pancreatic ribonuclease family - Wikipedia

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(Redirected from Ribonuclease A)

Pancreatic ribonuclease

Structure of RNase A

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Pancreatic ribonuclease

Identifiers

Symbol

RNaseA

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	PDB: 11ba PDB: 11bg PDB: 1a2w PDB: 1a4y PDB: 1a5p PDB: 1a5q PDB: 1afk PDB: 1afl PDB: 1afu PDB: 1agi

Pancreatic ribonuclease family (EC 4.6.1.18, 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) is a superfamily of 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.

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] The human genome contains 8 genes that share the structure and function with bovine pancreatic ribonuclease, with 5 additional pseudo-genes. The structure and dynamics of these enzymes are related to their diverse biological functions.^[3]

Other proteins belonging to the pancreatic ribonuclease superfamily include: bovine seminal vesicle and brain ribonucleases; kidney non-secretory ribonucleases;^[4] liver-type ribonucleases;^[5] angiogenin, which induces vascularisation of normal and malignant tissues; eosinophil cationic protein,^[6] 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.^[7]

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.^[8] Pancreatic ribonucleases that are not inhibited by RI are approximately as toxic as alpha-sarcin, diphtheria toxin, or ricin.^[9]

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.^[10] 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.^[11]

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. S2CID 21907373.
^ 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. S2CID 2905312.
^ Narayanan C, Bernard DN, Bafna K, Gagné D, Chennubhotla CS, Doucet N, Agarwal PK (Mar 2018). "Conservation of Dynamics Associated with Biological Function in an Enzyme Superfamily". Structure. 26 (3): 426–436. doi:10.1016/j.str.2018.01.015. PMC 5842143. PMID 29478822.
^ 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. Bibcode:1989PNAS...86.4460R. 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. doi:10.1016/S0021-9258(18)54842-0. 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

Hydrolase: esterases (EC 3.1)

3.1.1: Carboxylic
ester hydrolases

Lipase

Phospholipase
- A1
- A2
- B

3.1.2: Thioesterase

3.1.3: Phosphatase

3.1.4:
Phosphodiesterase

3.1.6: Sulfatase

Nuclease (includes
deoxyribonuclease
and ribonuclease)

3.1.11-16:
Exonuclease

Exodeoxyribonuclease	RecBCD
Exoribonuclease	Oligonucleotidase

3.1.21-31:
Endonuclease

Endodeoxyribonuclease	Deoxyribonuclease I Deoxyribonuclease II Deoxyribonuclease IV Restriction enzyme;see {{Restriction enzyme}} UvrABC endonuclease
Endoribonuclease	RNase III Drosha: Microprocessor complex Dicer: RNA-induced silencing complex RNase H 1 2A 2B 2C RNase P RNase A RNase Z RNase E 1 2 3 4/5 RNase T1
either deoxy- or ribo-	Nuclease S1 Mung bean nuclease Serratia marcescens nuclease Micrococcal nuclease

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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