Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sensitive RNase mapping technique was used to investigate the expression of individual class I mRNA in the embryo and placenta of the mouse from day 7.5 through day 13 of gestation. Transcripts of the H-2Kd and -Dd genes appeared in both placental and embryonic tissues as early as day 7.5 post coitum and continued to be expressed thereafter. In contrast, H-2Ld mRNA was barely detectable in embryonic RNA until day 18 of pregnancy, although it was present in placental RNA samples on days 10 to 13 of gestation. Qa-region genes demonstrated a different pattern of expression than H-2Dd, -Kd, and -Ld. Transcripts of Q7, one of the genes encoding Qa-2 surface Ag, were detected in the developing embryo on days 9 to 11 post coitum but decreased thereafter. However, Q7d transcripts were not detected in placental tissues at any stage. Q6 mRNA was not detected in any of the tissues, and Q10 mRNA was detected only in day 12 to 13 embryos, where expression is known to be restricted to the fetal liver. Transcripts from T13, a Tla-region gene, and D2d, a D-region gene, were not detected in any of the samples tested. This study has revealed a complex pattern of class I gene regulation both within the genes of the MHC and between the embryo and placental lineages during the midgestational stages of development.
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PMID:Differential expression of the class I MHC genes in the embryo and placenta during midgestational development in the mouse. 271 43

Bovine seminal ribonuclease (BS RNase) displays immunosuppressive and antitumor activities on mammalian cells, whereas bovine pancreatic ribonuclease (RNase A) is not cytotoxic. To learn more about the mechanism of BS RNase cytotoxicity, various mutants and hybrid proteins were prepared. A series of RNase A variants substituted with amino acid residues from BS RNase were prepared. Concerning quaternary structure, a significant impact was achieved in the variant TM (Q28L K31C S32C), which forms a dimer joined covalently by two intersubunit disulfide bonds. This variant is more efficient than RNase A but less active than BS RNase. Introduction of cationic residues at positions 55, 62, and 64 or substitution at positions 111 and 113 enhanced the immunosuppressive activity of RNase A but did not confer its antitumor activity. The substitution at positions 28, 31, 32, 55, 62, 64, 111, and 113 in variant T13 exerted the best immunosuppressive and antitumor effect observed among the round of the RNase A variants. Replacement of the active-site histidine residues H12 and H119 with asparagine led to the loss of both catalytic and biological activities. Five previously prepared hybrid enzymes (SRA 1-5), synthesized by introducing 16 amino acid residues from RNase A into BS RNase, exerted the same immunosuppressive activities as did the wild-type BS RNase. However, the substitution at positions 111, 113, and 115 in variant SRA 5 caused a marked decrease in its antitumor effect, indicating that these residues play an important role in antitumor efficiency. A different mechanism of action of RNases on tumor cells and/or on blastogenic transformed lymphocytes has been assumed.
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PMID:Structural changes to ribonuclease A and their effects on biological activity. 1044 19

The ribonuclease (RNase) A superfamily lineage includes distant members with antimicrobial properties, suggesting a common ancestral host-defense role. In an effort to identify the minimal requirements for the eosinophil cationic protein (ECP or RNase 3) antimicrobial properties we applied site-directed mutagenesis on its closest family homolog, the eosinophil-derived neurotoxin (EDN or RNase 2). Both eosinophil secretion proteins are involved in human immune defense, and are reported as being among the most rapidly evolving coding sequences in primates. Previous studies in our laboratory defined two regions at the N-terminus involved in the protein antimicrobial action, encompassing residues 8-16 and 34-36. Here, we demonstrate that switching two single residues is enough to provide EDN with ECP antipathogen properties. That is, the EDN double-mutant Q34R/R35W displays enhanced bactericidal activity, particularly towards Gram-negative bacteria, and a significant increase in its affinity towards the bacterial outer membrane lipopolysaccharides. Moreover, we confirmed the direct contribution of residue W35 in lipopolysaccharide binding, membrane interaction and permeabilization processes. Furthermore, additional T13 to I substitution provides EDN with an exposed hydrophobic patch required for protein self-aggregation and triggers bacterial agglutination, thereby increasing the final antimicrobial activity by up to 20-fold. Our results highlight how single selected mutations can reshape the entire protein function. This study provides an example of how structure-guided protein engineering can successfully reproduce an evolution selection process towards the emergence of new physiological roles.
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PMID:Towards the rational design of antimicrobial proteins: single point mutations can switch on bactericidal and agglutinating activities on the RNase A superfamily lineage. 2399 92