Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urine contains nondialyzable inhibitors of calcium oxalate crystal growth. We have pursued the hypothesis that these inhibitors may, in part, be acidic peptides and polyribonucleotide fragments. Homopolyribonucleotides and RNA inhibit calcium oxalate crystal growth at 5 x 10(-6) M of constituent ribonucleotide, whereas the monomer nucleotides are inactive at 10(-4) M. Poly-L-aspartic or glutamic acid are also inhibitory at 5 X 10(-6) M of amino acid, whereas the monomeric amino acids are inert. Gastric pepsin, a naturally occurring acidic peptide, is inhibitory. Incubation with nonspecific protease reduced the inhibitory effectiveness of normal human urine consistently and significantly, a fact compatible with an important contribution of peptides. A variable additional reduction was produced by subsequent treatment with ribonuclease, suggesting only a small role for polyribonucleotide. Sequential ion exchange and gel filtration chromatography and preparative disc gel electrophoresis yielded inhibitory material enriched with peptides that were strongly acidic and high in proline. Peptides and ribonucleotides seem to contribute to urinary nondialyzable crystal growth inhibitory activity.
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PMID:Acidic peptide and polyribonucleotide crystal growth inhibitors in human urine. 92 Aug 14

1. The crystal growth inhibitory activity of mixtures of known inhibitors and of mixtures of known inhibitors with normal urine was determined in calcium oxalate monohydrate and hydroxyapatite seeded crystal growth systems. 2. The inhibitory activity of the mixtures was compared with the measured activity of the individual components of the mixtures. All mixtures had inhibitory activity equal to the sum of the activities of their components, with the exception of RNA/urine mixtures in the calcium oxalate monohydrate system. 3. RNA/urine mixtures had inhibitory activity toward calcium oxalate monohydrate crystal growth which was less than would be predicted from the activity of the RNA and of the urine which were added. This reduced inhibitory activity was shown to be due probably to hydrolysis of RNA by the ribonuclease activity normally present in urine. 4. The results of these experiments make it possible to determine quantitatively the contribution of various naturally occurring urinary crystal growth inhibitors to the total measured inhibition observed in urine.
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PMID:Urinary crystal growth: effect of inhibitor mixtures. 616 79

4-Hydroxy-4-methyl-2-oxoglutarate (HMG)/4-carboxy-4-hydroxy-2-oxoadipate (CHA) aldolases are class II (divalent metal ion dependent) pyruvate aldolases from the meta cleavage pathways of protocatechuate and gallate. The enzyme from Pseudomonas putida F1 is structurally similar to a group of proteins termed regulators of RNase E activity A (RraA) that bind to the regulatory domain of RNase E and inhibit the ribonuclease activity in certain bacteria. Analysis of homologous RraA-like proteins from varying species revealed that they share sequence conservation within the active site of HMG/CHA aldolase. In particular, the P. putida F1 HMG/CHA aldolase has a D-X20-R-D motif, whereas a G-X20-R-D-X2-E/D motif is observed in the structures of the RraA-like proteins from Thermus thermophilus HB8 (TtRraA) and Saccharomyces cerevisiae S288C (Yer010Cp) that may support metal binding. TtRraA and Yer010Cp were found to contain HMG aldolase and oxaloacetate decarboxylase activities. Similar to the P. putida F1 HMG/CHA aldolase, both TtRraA and Yer010Cp enzymes required divalent metal ions for activity and were competitively inhibited by oxalate, a pyruvate enolate analogue, suggesting a common mechanism among the enzymes. The RraA from Escherichia coli (EcRraA) lacked detectable C-C lyase activity. Upon restoration of the G-X20-R-D-X2-E/D motif, by site-specific mutagenesis, the EcRraA variant was able to catalyze oxaloacetate decarboxylation. Sequence analysis of RraA-like gene products found across all the domains of life revealed conservation of the metal binding motifs that can likely support a divalent metal ion-dependent enzyme reaction either in addition to or in place of the putative RraA function.
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PMID:Biochemical and structural analysis of RraA proteins to decipher their relationships with 4-hydroxy-4-methyl-2-oxoglutarate/4-carboxy-4-hydroxy-2-oxoadipate aldolases. 2435 11