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)

Fabry disease is an X-linked disorder accompanied with accumulation of glycosphingolipids resulting from the deficient activity of the lysosomal hydrolase, alpha-galactosidase A (alpha-GalA). In the present study, mRNA for alpha-GalA in fibroblasts from an 11-year-old Japanese patient with Fabry disease was examined using the reverse transcriptase-polymerase chain reaction (PCR). The shorter message of alpha-GalA was demonstrated in this patient when compared with the normal control. The complete deletion of exon 4 in the mRNA for alpha-GalA in the patient was disclosed by analysis of cDNA with restriction enzyme digestion and asymmetrical PCR sequencing. The direct sequencing of the genomic DNA demonstrated a single base substitution (G----A) at the 3' end of the consensus sequence of intron 3. This mutation destroyed a splice site in the alpha-GalA, which produced a mutant allele. It was also shown that the mother of the patient had this mutant as well as normal alleles as a heterozygote.
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PMID:A 3' splice site consensus sequence mutation in the intron 3 of the alpha-galactosidase A gene in a patient with Fabry disease. 175 37

We have investigated in detail the secondary and tertiary structures of E. coli 16S rRNA binding site of protein S15 using a variety of enzymatic and chemical probes. RNase T1 and nuclease S1 were used to probe unpaired nucleotides and RNase V1 to monitor base-paired or stacked nucleotides. Bases were probed with dimethylsulfate (at A(N-1), C(N-3) and G(N-7)), with 1-cyclohexyl-3 (2-(1-methylmorpholino)-ethyl)-carboiimide-p- toluenesulfonate (at U(N-3) and G(N-1)) and with diethylpyrocarbonate (at A(N-7)). The RNA region corresponding to nucleotides 652 to 753 was tested within: (1) the complete 16S rRNA molecule; (2) a 16S rRNA fragment corresponding to nucleotides 578 to 756 obtained by transcription in vitro; (3) the S15-16S rRNA complex; (4) the S15-fragment complex. Cleavage and modification sites were detected by primer extension with reverse transcriptase. Our results show that: (1) The synthetized fragment folds into the same overall secondary structure as in the complete 16S rRNA, with the exception of the large asymmetrical internal loop (nucleotides 673-676/714-733) which is fully accessible in the fragment while it appears conformationally heterogeneous in the 16S rRNA; (2) the reactivity patterns of the S15-16S rRNA and S15-fragment complexes are identical; (3) the protein protects defined RNA regions, located in the large interior loop and in the 3'-end strand of helix [655-672]-[734-751]; (4) the protein also causes enhanced chemical reactivity and enzyme accessibility interpreted as resulting from a local conformational rearrangement, induced by S15 binding.
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PMID:The E. coli 16S rRNA binding site of ribosomal protein S15: higher-order structure in the absence and in the presence of the protein. 245 25

The aim of this study has been to determine the distribution of somatic mutations in the 5' flanking regions of rearranged immunoglobulin heavy chain variable region genes (VDJ). We sequenced the 5' flanking region in 12 secondary immune response antibodies produced in C57BL/6j mice against the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken-gamma-globulin. In these and previously published sequences, almost 97% of the mutations occurred in the transcribed region of the gene, and only a minority of genes (5/29) contained mutations upstream of the transcription start (cap) site. No potential germ-line donor was found for a cluster of five base changes previously found in a single heavy chain gene, 3B62. However, the uniqueness of this mutational cluster and its distance from the normally mutated region suggests that the nucleotide changes may not be due to the normal mutator mechanism. Thus, as this was the only instance of somatic mutations that far upstream of the promoter/cap site region, the reverse transcriptase model for somatic hypermutation is still a possibility. The data are consistent with a mutational mechanism that requires transcription of the rearranged target V(D)J gene which appears to result in the generation of a positively skewed asymmetrical distribution of somatic mutations. A single mode is centered near the V(D)J and a long tail extends into the 3' non-translated region of the J-C intron. Two classes of model could explain this mutation distribution pattern: those where transcription products (RNA, cDNA) are the direct mutational substrates, or those that postulate local unfolding of the chromatin around a V(D)J rearrangement directly exposing the DNA of the transcribed region to specific mutational enzymes.
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PMID:Somatic hypermutation in 5' flanking regions of heavy chain antibody variable regions. 837 Mar 98

The reverse transcriptase (RT) of HIV which has been inhibited by the incorporation of AZT into the primer strand is subject to a deblocking reaction by cellular ATP. This reaction yields unblocked primer plus the dinucleoside tetraphosphate, AZTp(4)A. In the present study, we report that AZTp(4)A is an excellent substrate for the enzyme Ap(4)A hydrolase (asymmetrical dinucleoside tetraphosphatase, EC 3.6.1.17), an enzyme that is widely distributed in many cell types. Progress of the reaction has been monitored by 31P NMR, and it was found that hydrolysis results in the production of AZTTP:ATP in a 7:1 ratio. The AZTp(4)A was also hydrolyzed at a rate 1.8-fold more rapidly than Ap(4)A. Spectrophotometric assays yielded Michaelis constants of 2.35 and 0.71 microM for Ap(4)A and AZTp(4)A, respectively. It, therefore, appears that Ap(4)A hydrolase can play a useful role in the regeneration of the AZTTP, the active form of AZT, for the inhibition of HIV RT.
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PMID:Metabolic transformation of AZTp4A by Ap4A hydrolase regenerates AZT triphosphate. 1276 70