Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluoride acts as a noncompetitive, strong inhibitor of (asymmetrical) Ap4A hydrolases (EC 3.6.1.17). The Ki values estimated for the enzymes isolated from seeds of some higher plants (yellow lupin, sunflower and marrow) are in the range of 2-3 microM and I50 for the hydrolase from a mammalian tissue (beef liver) is 20 microM. The anion, up to 25 mM, does not affect the following other enzymes which are able to degrade the bis(5'-nucleosidyl)-oligophosphates: Escherichia coli (symmetrical) Ap4A hydrolase (EC 3.6.1.41), yeast Ap4A phosphorylase (EC 2.7.7.53), yellow lupin Ap3A hydrolase (EC 3.6.1.29) and phosphodiesterase (EC 3.1.4.1). None of halogenic anions but fluoride affects the activity of (asymmetrical) Ap4A hydrolases. Usefulness of the fluoride effect for the in vivo studies on the Ap4A metabolism is shortly discussed.
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PMID:Fluoride is a strong and specific inhibitor of (asymmetrical) Ap4A hydrolases. 215 11

The different patterns of enzymatic cleavage of diadenosine polyphosphates, ApnAs, where n = 3-5, have been established by fast atom bombardment mass spectrometry, FAB MS, of the nucleotide products formed in the presence of H2(18)O. The three specific pyrophosphohydrolases, Ap3A hydrolase (EC 3.6.1.29) and (asymmetrical) Ap4A hydrolase (EC 3.6.1.17) from lupin and the (symmetrical) Ap4A hydrolase (EC 3.6.1.41) from Escherichia coli, manifest three different regiospecificities. The Ap3A hydrolase cleaves all four substrates tested, Ap3A, Ap4A, ApCH2ppA, and ApCHFppA, to give [18O]AMP and the corresponding unlabeled adenosine nucleotide. In each case, the enzyme cleaves at the phosphate proximate to the bound adenosine moiety. The (asymmetrical) Ap4A hydrolase cleaves both Ap4A and Ap5A to give unlabeled ATP plus [18O]AMP and [18O]ADP, respectively, and is thus seen to add water at the fourth phosphate from the bound adenosine moiety. Lastly, the (symmetrical) Ap4A hydrolase from E. coli gives beta-[18O]ADP from Ap3A, Ap4A, and Ap5A along with the unlabeled nucleotide coproducts. In addition, with Ap4A alpha S (ApspppA) as substrate for the bacterial enzyme, the products are beta-[18O]ADP and unlabeled ADP alpha S. This symmetrical enzyme is thus characterized as cleaving the polyphosphate chain at the second phosphate from the bound adenosine moiety.
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PMID:Regiospecificity of the hydrolysis of diadenosine polyphosphates catalyzed by three specific pyrophosphohydrolases. 828 47

A 200-300 kb region of chromosome 3p14.2, including the fragile site locus FRA3B, is homozygously deleted in multiple tumor-derived cell lines. Exon amplification from cosmids covering this deleted region allowed identification of the human FHIT gene, a member of ther histidine triad gene family, which encodes a protein with 69% similarity to an S. pombe enzyme, diadenosine 5', 5''' P1, P4-tetraphosphate asymmetrical hydrolase. The FHIT locus is composed of ten exons distributed over at least 500 kb, with three 5' untranslated exons centromeric to the renal carcinoma-associated 3p14.2 breakpoint, the remaining exons telomeric to this translocation breakpoint, and exon 5 within the homozygously deleted fragile region. Aberrant transcripts of the FHIT locus were found in approximately 50% of esophageal, stomach, and colon carcinomas.
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PMID:The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. 859 45