Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is shown by fluorescence spectroscopy that the post-activated form of neocarzinostatin chromophore (NCSi-glu) can form stable complexes with single-site oligonucleotides (SSOs) featuring sequences known to be involved in double stranded (AGC.GCT, AGT.ACT, AGA.TCT, ACA.TGT) or single stranded (AGG.CCT) cleavage (attacked residues in bold). Furthermore, the same SSOs form cleavage productive complexes with native neocarzinostatin chromophore (NCS chrom) over a similar concentration range. The productive complexes yield damage similar to that observed if the same sequence is part of a longer DNA piece. Previously identified double stranded site sequences ATT.AAT and TAT.ATA are shown to contain overlapping attack sites. Binding order preference derived from fluorescence quenching experiments for NCSi-glu is consistent with constants derived by quantitative cleavage affinity binding experiments with NCS chrom. This confirms the similarity in interactions between the NCSi-glu and NCS chrom and justifies the use of NCSi-glu as a stable analog of NCS chrom.
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PMID:Binding and cleavage characteristics of the complexes formed between the neocarzinostatin chromophore and single site containing oligonucleotides. 758 49

Mutation of six residues of Escherichia coli aspartate aminotransferase results in substantial acquisition of the transamination properties of tyrosine amino-transferase without loss of aspartate transaminase activity. X-ray crystallographic analysis of key inhibitor complexes of the hexamutant reveals the structural basis for this substrate selectivity. It appears that tyrosine aminotransferase achieves nearly equal affinities for a wide range of amino acids by an unusual conformational switch. An active-site arginine residue either shifts its position to electrostatically interact with charged substrates or moves aside to allow access of aromatic ligands.
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PMID:Alternating arginine-modulated substrate specificity in an engineered tyrosine aminotransferase. 766 15

A new HLA-B18 allele (B*1802) derived from a Thai individual was sequenced. Comparison of this B18 nucleotide sequence with the published B*1801 sequence indicated that this Asian B18 allele has a nucleotide sequence different from that of B*1801. Three nucleotide changes were observed in exon 3, in which two substitutions at codon 97, AGG in B*1801 to AAT in the B*1802, result in an amino acid change from arginine to asparagine. The residue 97Asn has also been described in some B27 subtypes. A silent mutation was also observed at codon 99, TAC in B*1801 to TAT in the B*1802. This sequence has been reported in many class I alleles published so far. Moreover, 18 HLA-B18-positive samples were examined by the PCR-SSO method using specific probes for B*1801 and B*1802. The results demonstrated that three Asian samples possess B*1802 and share HLA-Cw7, DR12, and DQ7.
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PMID:A new B18 sequence (B*1802) from Asian individuals. 775 Nov 57

Triplex-forming oligodeoxyribonucleotides (TFOs) can be designed so as to form antiparallel triple helices with duplex DNA by means of GGC and TAT or AAT base triplets, and these have been shown to be useful as sequence-specific DNA binding agents. Using TFOs targeted to the promoter region of the rat neu oncogene, it is shown here that substitution of an imidazole-nucleoside chimera at a single site in a neu specific TFO results in an increase in TFO binding affinity and specificity. This effect is discussed in terms of the stabilizing effect of local imidazole-TA triplet formation. It is also found that site-selective substitution of 2'-deoxy-6-thioguanosine for guanosine (S6-dG) in the TFO results in an increase in triplex formation in the presence of physiological levels of potassium ion. The utility and positioning of S6-dG base substitutions is discussed in the context of an intramolecular tetrad model.
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PMID:Triplex formation at the rat neu gene utilizing imidazole and 2'-deoxy-6-thioguanosine base substitutions. 784 62

hisH encodes imidazole acetol phosphate (IAP) aminotransferase in Zymomonas mobilis and is located immediately upstream of tyrC, a gene which codes for cyclohexadienyl dehydrogenase. A plasmid containing hisH was able to complement an Escherichia coli histidine auxotroph which lacked the homologous aminotransferase. DNA sequencing of hisH revealed an open reading frame of 1,110 bp, encoding a protein of 40,631 Da. The cloned hisH product was purified from E. coli and estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to have a molecular mass of 40,000 Da. Since the native enzyme had a molecular mass of 85,000 Da as determined by gel filtration, the active enzyme species must be a homodimer. The purified enzyme was able to transaminate aromatic amino acids and histidine in addition to histidinol phosphate. The existence of a single protein having broad substrate specificity was consistent with the constant ratio of activities obtained with different substrates following a variety of physical treatments (such as freeze-thaw, temperature inactivation, and manipulation of pyridoxal 5'-phosphate content). The purified enzyme did not require addition of pyridoxal 5'-phosphate, but dependence upon this cofactor was demonstrated following resolution of the enzyme and cofactor by hydroxylamine treatment. Kinetic data showed the classic ping-pong mechanism expected for aminotransferases. Km values of 0.17, 3.39, and 43.48 mM for histidinol phosphate, tyrosine, and phenylalanine were obtained. The gene structure around hisH-tyrC suggested an operon organization. The hisH-tyrC cluster in Z. mobilis is reminiscent of the hisH-tyrA component of a complex operon in Bacillus subtilis, which includes the tryptophan operon and aroE. Multiple alignment of all aminotransferase sequences available in the database showed that within the class I superfamily of aminotransferases, IAP aminotransferases (family I beta) are closer to the I gamma family (e.g., rat tyrosine aminotransferase) than to the I alpha family (e.g., rat aspartate aminotransferase or E. coli AspC). Signature motifs which distinguish the IAP aminotransferase family were identified in the region of the active-site lysine and in the region of the interdomain interface.
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PMID:Imidazole acetol phosphate aminotransferase in Zymomonas mobilis: molecular genetic, biochemical, and evolutionary analyses. 788 15

The substrate specificity of tyrosine aminotransferase (eTAT) from Escherichia coli has been tested by transferring the critically different residues Leu39, Glu141, and Arg293 into equivalent positions of aspartate aminotransferase (eAAT). These residues are not directly involved in the catalytic process. The single mutant eAAT V39L possesses greater values of kcat/KM not only for tyrosine but also for aspartate and glutamate. In contrast, the double mutant eAAT P141E,A293R and also the triple mutant eAAT V39L,P141E,A293R exhibit smaller changes of kcat/KM. The converse mutants of tyrosine aminotransferase, in which critical residues of eAAT (Val39) and of mitochondrial AAT (Ala39, Val37) were transferred into equivalent positions of eTAT, exhibited generally decreased values of kcat/KM for both dicarboxylic and aromatic substrates. On the basis of the known structures of eAAT and eAAT V39L as well as of a refined model of eTAT, these results indicate that the different substrate specificities of eAAT and eTAT are due to multiple side chain differences and minor rearrangements of the backbone. The generally improved catalytic efficiency of the mutant eAAT V39L appears to be due to an indirect effect, namely, the facilitated closure of the active site upon substrate binding.
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PMID:Significant improvement to the catalytic properties of aspartate aminotransferase: role of hydrophobic and charged residues in the substrate binding pocket. 790 77

The cytosolic and mitochondrial isozymes of aspartate aminotransferase (AspAT) function in the C4 photosynthetic cycle in NAD-malic enzyme-type C4 plants and are expressed at high levels in mesophyll cells and bundle sheath cells, respectively. We constructed a genomic library from Panicum miliaceum, a NAD-malic enzyme-type C4 plant, and cloned the genes for these isozymes. The sequence of the cloned gene for cytosolic AspAT spans 7800 bp and consists of 12 exons. The sequence of the cloned gene for mitochondrial AspAT spans 9000 bp and consists of 10 exons. The results of primer-extension analysis suggest that transcription may be initiated from multiple adjacent sites. Both genes have significant GC-rich regions around the site of initiation of transcription, and these regions showed no CpG suppression. The 5'- flanking regions of both genes include several short sequences similar to the regulatory elements found in other genes for components of the photosynthetic machinery. In particular, the cytosolic AspAT gene contains sequences similar to nuclear protein-binding sites in other mesophyll-expressed C4 photosynthetic genes and the mitochondrial AspAT gene contains elements for light-sensitive and constitutive expression of a bundle sheath-expressed gene. The results of Southern analysis indicated that there are at least two genes that encode each isozyme in the genome of P. miliaceum. A comparison of intron-insertion positions between AspAT genes of plants and animals revealed that several introns are located at identical positions. On the basis of a phylogenetic tree among AspATs and tyrosine aminotransferase, we have shown that the introns of aminotransferase genes antedate the divergence of eubacteria, archaebacteria, and eukaryotes.
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PMID:Structure of genes that encode isozymes of aspartate aminotransferase in Panicum miliaceum L., a C4 plant. 794 26

The 61 codons and the three terminators were counted in the coding sequences of 31 families of proteins of higher vertebrates. The protein families were ordered according to their evolutionary rate. In each family, the ratio between the Observed and Expected frequency of each codon was obtained (O/E ratio). A strong and significant positive correlation was observed between the O/E ratio of the eight codons AAC, TAT, ATA, GAA, ACA, AAT, ATG and CGA and the evolutionary rate of the protein. A negative and significant correlation was observed for codons AAG and GAG. It was advanced that the functional constraints of proteins can influence the usage of codons, particularly for those trimers which are components of signal sequences. It was also observed that the O/E ratios of the terminators are negatively correlated with the evolutionary rate of the protein they terminate, and the correlation is significant for TAA and TGA, which in vertebrates might be older than TAG.
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PMID:Codon usage and evolutionary rates of proteins. 815 18

Although several high-resolution X-ray crystallographic structures have been determined for Escherichia coli aspartate aminotransferase (eAATase), efforts to crystallize E. coli tyrosine aminotransferase (eTATase) have been unsuccessful. Sequence alignment analyses of eTATase and eAATase show 43% sequence identity and 72% sequence similarity, allowing for conservative substitutions. The high similarity of the two sequences indicates that both enzymes must have similar secondary and tertiary structures. Six active site residues of eAATase were targeted by homology modeling as being important for aromatic amino acid reactivity with eTATase. Two of these positions (Thr 109 and Asn 297) are invariant in all known aspartate aminotransferase enzymes, but differ in eTATase (Ser 109 and Ser 297). The other four positions (Val 39, Lys 41, Thr 47, and Asn 69) line the active site pocket of eAATase and are replaced by amino acids with more hydrophobic side chains in eTATase (Leu 39, Tyr 41, Ile 47, and Leu 69). These six positions in eAATase were mutated by site-directed mutagenesis to the corresponding amino acids found in eTATase in an attempt to redesign the substrate specificity of eAATase to that of eTATase. Five combinations of the individual mutations were obtained from mutagenesis reactions. The redesigned eAATase mutant containing all six mutations (Hex) displays second-order rate constants for the transamination of aspartate and phenylalanine that are within an order of magnitude of those observed for eTATase. Thus, the reactivity of eAATase with phenylalanine was increased by over three orders of magnitude without sacrificing the high transamination activity with aspartate observed for both enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Redesign of the substrate specificity of Escherichia coli aspartate aminotransferase to that of Escherichia coli tyrosine aminotransferase by homology modeling and site-directed mutagenesis. 852 73

Male rats of Wistar SPF stain (Velaz Prague) were used to investigate the influence of prolonged starvation on changes in the activity of selected adaptive enzymes in the liver and corticosterone in serum. Analyses were carried out on days 1,2,3,5 and 7 of starvation. The activity of tyrosine aminotransferase significantly increased in the period between days 2 and 5 of starvation, after which a decrease to the level of satiated animals was observed in the terminal period. Activities of tryptophane-2-3-dioxygenase and alanine aminotransferase increased in two phases reaching maximum values on days 2 and 7 of starvation. The activity of aspartate aminotransferase showed a progressive significant increase in dependence on the length of starvation. A more than threefold increase in corticosterone concentration was observed in the serum of starved animals in comparison with satiated rats.
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PMID:[The effect of prolonged starvation on changes in the activity of selected adaptive enzymes in rat liver]. 862 17


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