Ribonuclease inhibition

In a study of the inhibition of components of the cytochrome systems by maeromolecular poly-ions, Person and Fine205-20 showed that such polycations as protamine sulfate, histone, and ribonuclease inhibit the cytochrome oxidase activity of various systems. The inhibition could be reversed by the addition- of poly-ions (and, especially, by polyglucose sulfate) the latter was also shown to inhibit the oxidase system reversibly. 

Pouckova P, Zadinova M, Hlouskova D, Strohalm J, Plocova D, Spunda M, Olejar T, Zitko M, Matousek J, Ulbrich K, Soucek J. Polymer-conjugated bovine pancreatic and seminal ribonucleases inhibit growth of human tumors in nude mice. J Cont Rel 2004 95 83-92. 

J. Sou k, P. PouCkovd, M. Zadinov, D. Hlouskov, D. Plocov, J. Strohalm, Z. Hrkal, T. Olej r and K. Ulbrich, Polymer conjugated bovine seminal ribonuclease inhibits growth of solid tumors and development of metastases in mice. Neoplasma, 48, 127-132 (2001). 

However, there are a number of other miscellaneous biological roles played by this complex. The [Co(NH3)6]3+ ion has been shown to inhibit the hammerhead ribozyme by displacing a Mn2+ ion from the active site.576 However, [Co(NH3)6]3+ does not inhibit ribonuclease H (RNase),577 topoisomerase I,578 or hairpin ribozyme,579 which require activation by Mg2+ ions. The conclusions from these studies were that an outer sphere complex formation between the enzyme and Mgaq2+ is occuring rather than specific coordination of the divalent ion to the protein. These results are in contrast to DNase I inhibition by the same hexaammine complex. Inhibition of glucose-induced insulin secretion from pancreatic cells by [Co(NH3)6]3+ has been found.580 Intracellular injection of [Co(NH3)6]3+ into a neurone has been found to cause characteristic changes to the structure of its mitochondria, and this offers a simple technique to label neuronal profiles for examination of their ultrastructures.581... 

It was shown that polyglucose splfate could reverse the inhibition, by polymyxin or ribonuclease, of the tumor-damaging effect of endotoxins from Serratia marcescens.m It was also demonstrated that polyglucose sulfate abolishes the ability of lysozyme to lower the fever-producing activity of the bacterial polysaccharide from the same organism. 

The five N-terminal residues and the six or seven C-terminal residues cannot be seen in the high resolution electron density map, and the loop referred to above, formed by residues 44 to 53, appears at only one-third to one-half the amplitude of the well-resolved parts of the map. The lack of clarity in these three regions might possibly result from poor phasing or some other crystallographic factor, but we consider it more likely that these predominantly hydrophilic sections of the peptide project in a disordered way into the solvent. In this connection, it is interesting that in the presence of Ca2+ and pdTp trypsin cleaves inhibited nuclease at only two points between residues 5 and 6 and between residues 48 and 49 (36-38) which are at the very extremity of the loop. It also seems relevant that ribonuclease S also shows lack of clarity at the ends of the peptide chains and in the region of a relatively exposed loop (56). 

The effects of inhibitors and activators on RNases Ti, N1 Ui, U2, and T2 are summarized in Table IV (5, 7, 8), showing the characteristics of each RNase. Ribonuclease Ti is strongly inhibited by 10 3M Zn2+ RNases and T2 are inhibited about half but RNases N and U2 are not inhibited. Ribonuclease T, is also strongly inhibited by 10 3M Ag+, while all other RNases are inhibited about half. But 10 3 M Cu2+ strongly inhibits RNase T2 and only about half inhibits the other RNases. All five RNases are not inhibited by 10 2 M ethylenediaminetetraacetate (EDTA) and 10-3 M ICH2COOH. No metallic cofactor is required for their action. 

The existence of a deoxyribonuclease in E. coli bound to an inhibitory RNA was first suggested by Kozloff (3< ) who found that the DNase activity of freshly prepared extracts could be markedly enhanced by pretreatment with ribonuclease. The enzyme was subsequently purified and freed of inhibitor (39). The purified enzyme termed endonuclease I could, in turn, be competitively inhibited by a variety of RNA s including transfer RNA, and Ri values as low as 10-8 M (nucleotide) have been observed (40). Examination of various purified RNA species and synthetic polyribonucleotides for their inhibitory activity has led... 

Boiziau, C., Larrouy, B., Moreau, S., Cazenave, C., Shire, D. and Toulme, J.-J. (1992a) Ribonuclease H-mediated inhibition of translation and reverse transcription by antisense oligodeoxynucleotides. Biochem. Soc. Transactions,... 

The enzymes used to generate reactive quinone methides often undergo inactivation by addition of this electrophile to essential nucleophilic amino acid side chains of the protein catalyst. This is a type of suicide enzyme inhibition.80 This was observed for the acid phosphatase and ribonuclease catalysts used to generate 43.76 79 Alkaline phosphatase has been used to remove the phosphate protecting group from a derivative of an o-difluoromethyl phenyl phosphate that was covalently attached to a solid support. Breakdown of the immobilized 4-hydroxybenzyl difluoride gives an immobilized quinone methide that, in principle, will react irreversibly with proteins and lead to their attachment to the solid support.81... 

Messmore, J.M. and R.T. Raines. 2000. Decavanadate inhibits catalysis by ribonuclease A. Biochim. Biophys. Acta 381 25-30. 

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