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Literature summary for 4.6.1.18 extracted from

  • Attery, A.; Dey, P.; Tripathi, P.; Batra, J.K.
    A ribonuclease inhibitor resistant dimer of human pancreatic ribonuclease displays specific antitumor activity (2018), Int. J. Biol. Macromol., 107, 1965-1970 .
    View publication on PubMed

Application

Application Comment Organism
pharmacology a recombinant ribonuclease-resistant dimeric variant of human pancreatic ribonuclease is generated which is specifically toxic to cancer cells. Combining dimerization of pancreatic ribonuclease-inhibitor-resistance results in providing potent anti-tumor activity to human pancreatic ribonuclease. The cytotoxic variants of human pancreatic ribonuclease will be useful in designing protein therapeutics with low immunogenicity Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli strain BL21 Codon Plus (x04DE3)-RIL Homo sapiens

Protein Variants

Protein Variants Comment Organism
K7A/N71A/E111A ribonuclease inhibitor-resistant cytotoxic variant Homo sapiens
additional information engineering of human pancreatic ribonuclease to develop two dimeric ribonuclease inhibitor-resistant molecules having anti-tumor activity. By incorporating two cysteines in human pancreatic ribonuclease and HPR-KNE (containing K7A/N71A/E111A mutations), a disulfide-linked dimeric pancreatic ribonuclease is generated, and a dimer of HPR-KNE, termed as HPR-D and HPR-KNE-D respectively. HPR-KNE-D is resistant towards inhibition by ribonuclease inhibitors, and is found to be highly toxic to a variety of cells. On J774A.1cells HPR-KNE-D is more than 375fold more cytotoxic than wild-type enzyme, and 15fold more toxic than HPR-D. Further,on U373 cells HPR-KNE-D is a more than 65fold more cytotoxic than HPR, and 9fold more toxic than HPR-D Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P07998
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
pancreas
-
Homo sapiens
-

Subunits

Subunits Comment Organism
monomer
-
Homo sapiens

Synonyms

Synonyms Comment Organism
HPR
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens

General Information

General Information Comment Organism
metabolism the enzyme lacks cytotoxic activity as it is inactivated by intracellular cytosolic ribonuclease inhibitor Homo sapiens