Disease relevance of yahJ

• Two mutations of the porphobilinogen (PBG) deaminase gene resulting in cross-reacting immunological material (CRIM) positive forms of acute intermittent porphyria (AIP) have been identified by in vitro amplification of cDNA and cloning of the amplified products in a bacterial expression vector [1].
• Recently, the biological relevance of assaying mammalian enzymes for DNA deaminase activity using Escherichia coli DNA as a reporter has been questioned, representing another round in the ongoing debate [2].
• Deoxycytidylate (dCMP) deaminase, a hexameric allosteric enzyme induced on infection of Escherichia coli by bacteriophage T4, was shown to contain two atoms of zinc per subunit by atomic absorption spectroscopy [3].
• The gene encoding melamine deaminase (TriA) from Pseudomonas sp. strain NRRL B-12227 was identified, cloned into Escherichia coli, sequenced, and expressed for in vitro study of enzyme activity [4].
• Proteus mirabilis amino acid deaminase: cloning, nucleotide sequence, and characterization of aad [5].

High impact information on yahJ

• Although this critically important enzyme shares common sequence motifs with apolipoprotein B mRNA-editing enzyme, and exhibits deaminase activity on free deoxycytidine in solution, it has not been shown to act on either RNA or DNA [6].
• Activation-induced cytidine deaminase (AID) is a single-stranded DNA deaminase required for somatic hypermutation of immunoglobulin (Ig) genes, a key process in the development of adaptive immunity [7].
• Here, we focus on mouse APOBEC2 (a muscle-specific protein for which we find no evidence of a deaminating activity on cytidine whether as a free nucleotide or in DNA) and mouse APOBEC3 (a DNA deaminase which we find widely expressed but most abundant in lymphoid tissue) [8].
• Cytidine (CR) deaminase was purified 47,000-fold to homogeneity from human placenta [9].
• Here we show that in Escherichia coli the APOBEC3G-induced cytidine deamination is inhibited by expression of Vif without depletion of deaminase [10].

Chemical compound and disease context of yahJ

• N-Acetylglucosamine 6-phosphate, an allosteric activator of the Escherichia coli deaminase, has no effect on the activity of the C. albicans enzyme [11].
• These results show that the interactions of Tyr254 are fundamental in coupling binding in the active site to events occurring in the allosteric pocket of E. coli glucosamine 6-P deaminase [12].
• Pseudomonas sp. strain ACP is capable of growth on 1-aminocyclopropane-1-carboxylate (ACC) as a nitrogen source owing to induction of the enzyme ACC deaminase and the subsequent conversion of ACC to alpha-ketobutyrate and ammonia (M. Honma, Agric. Biol. Chem. 49:567-571, 1985) [13].
• Recombinant f1 phages carrying a shuttle vector pKA1M for expression of blasticidin S deaminase were introduced into monkey COS7 cells by mixing with dioctadecylamidoglycylspermine (DOGS) [14].
• The treatment (0.05 U/ml of adenosine phosphate deaminase and apyrase) was applied to the detection of bacteria in broth by the L-L method, affording the detection of 42 colony-forming unit (CFU)/ml of Escherichia coli and 10 CFU/ml of Staphylococcus aureus in the broth [15].

Biological context of yahJ

• Studies are in progress to define the location of this nucleotide, which will be aided greatly by our recent clarification of the complete amino acid sequence of T2-deoxycytidylate deaminase [16].
• The Arabidopsis thaliana open reading frame At4g20960 predicts a protein whose N-terminal part is similar to the eubacterial 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate deaminase domain [17].
• The second atom of zinc is proposed to be located in a region of T4-dCMP deaminase that resembles a zinc finger [3].
• The crystallographic structure of the T state of Phe174-Ala deaminase, determined at 2.02 A resolution, shows no density for the segment 162-181, which is part of the active-site lid (PDB 1JT9) [18].
• On the basis of these cumulative findings, it has been possible to construct a mechanistic scheme for the deaminase reaction involving a single catalytic site which is able to catalyze the addition or removal of either NH3 or H2O [19].

Anatomical context of yahJ

• Attempts at overexpressing T4-phage deoxycytidylate deaminase using the pET3c/BL21(DE3)/pLysS system resulted in this enzyme being part of an inactive inclusion-body complex [20].
• In some of the newly identified DM domains, the glutamate is changed to a residue that could not function as a proton shuttle and in one instance (Mus musculus spermatid protein TENR) the cysteines are also changed to lysine and serine [21].

Associations of yahJ with chemical compounds

• However, on changing the arginine (Arg) at residue 115 of the T4-deaminase to either a glutamate (R115E) or a glutamine (R115Q), the resulting mutant enzymes were active in the absence of dCTP, with each mutant possessing a turnover number or k(cat) that is about 15% that of the wild-type deaminase [22].
• The deaminase is induced over 100-fold by GlcNAc and its level is about 0.3-0.5% of the proteins in crude extract [11].
• The deaminase has been crystallized through the use of polyethylene glycol; a scanning electron micrograph is presented [23].
• Another feature emphasizing the difference between the WT and mutant deaminases was observed on their denaturation-renaturation in EDTA, which revealed the mutants to be restored to 50% of their original activities with the WT deaminase only marginally restored [22].
• The NH2-terminal sequence (35 residues) determined from the purified deaminase was identical to the sequence of the deduced protein [11].

Other interactions of yahJ

• The structural gene for hemC is located within a 942bp sequence encoding the monomeric PBG deaminase, molecular weight 33,857 [24].
• Analysis of suppressor mutations rendering the mutant independent of amino sugar supply revealed that the catabolic enzyme D-glucosamine-6-phosphate isomerase (deaminase), encoded by gene nagB of the nag operon, was able to fulfill anabolic functions in amino sugar biosynthesis [25].
• Furthermore, a lacZ fusion with the ACC deaminase ORF resulted in the expression of active enzyme in E. coli [13].

Analytical, diagnostic and therapeutic context of yahJ

• Hybrid-selected translation and immunoprecipitation experiments revealed that the purified deaminase and the protein encoded by the clones were similar in size and in their antigenicity [11].
• Molecular weight analysis on the wild-type and mutant deaminases using HPLC size exclusion chromatography revealed that the wild-type deaminase was basically a hexamer, particularly in the presence of dCTP, regardless of the extent of dilution [22].
• Crystallization and preliminary X-ray diffraction studies of blasticidin S deaminase from Aspergillus terreus [26].
• Feeding rats a diet admixed with 500, 2000 and 8000 mg/kg body weight of DN-50000 for 35 days resulted in no significant dose-related changes in body weight, water consumption, urinalysis, haematological profiles, blood chemistry or histopathological profiles of either male or female rats from consumption of the enzyme preparation [27].
• The structure of the deaminase from Escherichia coli has been determined by X-ray crystallography at 1.9A resolution and gives important insight into the enzymic mechanism [28].

References