Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of rats with Cordycepin (3'-deoxyadenosine), an inhibitor of nuclear poly(A) synthesis, selectively decreased the energy and cytosol-dependent release of a portion of the mRNA species from the isolated hepatic nuclei in a cell-free system by approximately 40%. An analysis of the differential binding of the transported mRNA containing poly(A) tracts to nitrocellulose filters, and to cellulose or poly(U)-Sepharose columns suggested that the poly(A) tracts in the mRNA transported from the isolated hepatic nuclei of Cordycepin-treated rats, are decreased in size. This size decrease was confirmed through an analysis of the average size of the poly(A) tracts, released from the messengers by ribonuclease activity, on sucrose density gradients.
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PMID:Modified messenger ribonucleic acid release from isolated hepatic nuclei after inhibition of polyadenylate formation. 454 26

Treponema pallidum (Nichols strain), extracted in medium containing Eagle minimal essential medium 50% fresh, heat-inactivated normal rabbit serum, and 1.0 mM dithiothreitol, was incubated under 3% oxygen in the presence of tritiated nucleic acid precursors. [8-3H]adenine was incorporated with high efficiency into trichloroacetic acid-insoluble material; 2'-deoxyadenosine and uridine were incorporated in lower quantities, and thymine and thymidine were not incorporated. Incorporation of [3H]adenine was inhibited by penicillin G, mitomycin C, actinomycin D, and erythromycin, but was not affected by cycloheximide. Partial purification of nucleic acids from T. pallidum incubated with [8-3H]adenine for 36 to 72 h and subsequent treatment with ribonuclease and deoxyribonuclease revealed that 15 to 20% of the trichloroacetic acid-precipitable counts were resistant to ribonuclease but susceptible to deoxyribonuclease. A simple assay was developed in which NaOH treatment was used to distinguish incorporation into ribonucleic acid and deoxyribonucleic acid. Both ribonucleic acid and deoxyribonucleic acid synthesis continued for 6 days of incubation under 3% O2, whereas incorporation was limited to the first day of incubation in samples incubated under aerobic or anaerobic conditions. T. pallidum thus appears to be capable of significant de novo deoxyribonucleic acid and ribonucleic acid synthesis under microaerobic conditions.
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PMID:Long-term incorporation of tritiated adenine into deoxyribonucleic acid and ribonucleic acid by Treponema pallidum (Nichols strain). 615 24

Bovine seminal ribonuclease (BS-RNase) is a unique member of the pancreatic-like ribonuclease superfamily. This enzyme exists as two conformational isomers with distinctive biological properties. The structure of the major isomer is characterized by the swapping of the N-terminal segment (MxM BS-RNase). In this article, the crystal structures of the ligand-free MxM BS-RNase and its complex with 2'-deoxycitidylyl(3',5')-2'-deoxyadenosine derived from isomorphous crystals have been refined. Interestingly, the comparison between this novel ligand-free form and the previously published sulfate-bound structure reveals significant differences. In particular, the ligand-free MxM BS-RNase is closer to the structure of MxM BS-RNase productive complexes than to the sulfate-bound form. These results reveal that MxM BS-RNase presents a remarkable flexibility, despite the structural constraints of the interchain disulfide bridges and the swapping of the N-terminal helices. These findings have important implications to the ligand binding mechanism of MxM BS-RNase. Indeed, a population shift rather than a substrate-induced conformational transition may occur in the MxM BS-RNase ligand binding process.
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PMID:Population shift vs induced fit: the case of bovine seminal ribonuclease swapping dimer. 1504 72

A growing number of pancreatic-type ribonucleases (RNases) present cytotoxic activity against malignant cells. The cytoxicity of these enzymes is related to their resistance to the ribonuclease protein inhibitor (RI). In particular, bovine seminal ribonuclease (BS-RNase) is toxic to tumor cells both in vitro and in vivo. BS-RNase is a covalent dimer with two intersubunit disulfide bridges between Cys(31) of one chain and Cys(32) of the second and vice versa. The native enzyme is an equilibrium mixture of two isomers, MxM and M=M. In the former the two subunits swap their N-terminal helices. The cytotoxic action is a peculiar property of MxM. In the reducing environment of cytosol, M=M dissociates into monomers, which are strongly inhibited by RI, whereas MxM remains as a non-covalent dimer (NCD), which evades RI. We have solved the crystal structure of NCD, carboxyamidomethylated at residues Cys(31) and Cys(32) (NCD-CAM), in a complex with 2'-deoxycitidylyl(3'-5')-2'-deoxyadenosine. The molecule reveals a quaternary structural organization much closer to MxM than to other N-terminal-swapped non-covalent dimeric forms of RNases. Model building of the complexes between these non-covalent dimers and RI reveals that NCD-CAM is the only dimer equipped with a quaternary organization capable of interfering seriously with the binding of the inhibitor. Moreover, a detailed comparative structural analysis of the dimers has highlighted the residues, which are mostly important in driving the quaternary structure toward that found in NCD-CAM.
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PMID:Structure and stability of the non-covalent swapped dimer of bovine seminal ribonuclease: an enzyme tailored to evade ribonuclease protein inhibitor. 1519 98

We have previously demonstrated that an antibody-avidin fusion protein could be used to deliver biotinylated enzymes to tumor cells for antibody-directed enzyme prodrug therapy. However, the presence of the chicken protein avidin suggests that immunogenicity may be a problem. To address this concern, we developed a new delivery system consisting of human proteins. The amino-terminal 15-amino-acid peptide derived from human ribonuclease 1 (human S*tag) can bind with high affinity to human S*protein (residues 21-124 of the same ribonuclease). We constructed an antibody-S*protein fusion protein in which S*protein was genetically linked to an anti-rat transferrin receptor IgG3 at the carboxyl terminus of the heavy chain. We also constructed an enzyme-S*tag fusion protein in which S*tag was genetically linked to the carboxyl terminus of Escherichia coli purine nucleoside phosphorylase (PNP). When these two fusion proteins were mixed, S*tag and S*protein interacted specifically and produced homogeneous antibody/PNP complexes that retained the ability to bind antigen. Furthermore, in the presence of the prodrug 2-fluoro-2'-deoxyadenosine in vitro, the complex efficiently killed rat myeloma cells overexpressing the transferrin receptor. These results suggest that human ribonuclease-based site-specific conjugation can be used in vivo for targeted chemotherapy of cancer.
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PMID:An interaction between S*tag and S*protein derived from human ribonuclease 1 allows site-specific conjugation of an enzyme to an antibody for targeted drug delivery. 1591 91