Pancreatic ribonuclease family (, ''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
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The oth ...
-specific
endonucleases found in high quantity in the
pancreas
The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
of certain
mammals
A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...
and of some
reptiles.
Specifically, the enzymes are involved in endonucleolytic cleavage of 3'-phosphomono
nucleotides
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates. Ribonuclease can unwind the
RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
helix by complexing with single-stranded RNA; the complex arises by an extended multi-site cation-anion interaction between
lysine and
arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...
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
Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...
,
disulfide bond formation, protein
crystallography
Crystallography is the branch of science devoted to the study of molecular and crystalline structure and properties. The word ''crystallography'' is derived from the Ancient Greek word (; "clear ice, rock-crystal"), and (; "to write"). In J ...
and
spectroscopy
Spectroscopy is the field of study that measures and interprets electromagnetic spectra. In narrower contexts, spectroscopy is the precise study of color as generalized from visible light to all bands of the electromagnetic spectrum.
Spectro ...
, and
protein dynamics.
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.
Other proteins belonging to the pancreatic ribonuclease superfamily include: bovine seminal vesicle and brain ribonucleases; kidney non-secretory ribonucleases;
liver-type ribonucleases;
angiogenin, which induces vascularisation of normal and malignant tissues;
eosinophil cationic protein,
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.
Human genes
Human
Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...
genes
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
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
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Pa ...
for
ribonuclease inhibitor (RI), which protects cellular RNA from degradation by pancreatic ribonucleases. Pancreatic ribonucleases that are not inhibited by RI are approximately as toxic as
alpha-sarcin,
diphtheria toxin, or
ricin.
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
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
cells. Ranpirnase was studied in a
Phase III clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
as a treatment candidate for
mesothelioma, but the trial did not demonstrate statistical significance against primary endpoints.
References
{{Portal bar, Biology, border=no
Ribonucleases
EC 3.1.27
Protein domains