Disease relevance of cdd

• CRP/cAMP- and CytR-regulated promoters in Escherichia coli K12: the cdd promoter [1].
• Plaque forming lambda phages carrying the different cdd-lacZ fusions were isolated [2].
• Ribosomal -1 frameshifting during decoding of Bacillus subtilis cdd occurs at the sequence CGA AAG [3].
• Cytidine deaminase shows no detectable activity as a catalyst for the dehydration of 6-hydroxy-5,6-dihydrouridine [4].
• Three of five gastric carcinoma cell lines and five of eight colorectal cancer lines had increased levels of CDD mRNA following 24 h treatment with vitamin D3 [5].

High impact information on cdd

• Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site [6].
• Database-matched DNA sequences flanking the in vivo-protected Dam sites all fell in the non-coding regions of seven E. coli operons (mtl, cdd, flh, gut, car, psp and fep) [7].
• The activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class-switch recombination of Ig genes [8].
• In contrast to the situation in Escherichia coli, an L. lactis pyrG mutant could be constructed in the presence of a functional cdd gene encoding cytidine deaminase [9].
• Cytidine deaminase (CDA) is a zinc metalloenzyme that catalyzes the hydrolytic deamination of cytidine to uridine [10].

Chemical compound and disease context of cdd

• The sfiX gene (CS 44) has been identified as a homolog of the E. coli gene sanA, located downstream of the cytidine deaminase gene (cdd) [11].
• Cytidine deaminase, purified to homogeneity from constitutive mutants of Escherichia coli, was found to bind the competitive inhibitors pyrimidin-2-one ribonucleoside (apparent Ki = 3.6 x 10(-7) M) and 5-fluoropyrimidin-2-one ribonucleoside (apparent Ki = 3.5 x 10(-8) M) [12].
• Chromosomal location, cloning and nucleotide sequence of the Bacillus subtilis cdd gene encoding cytidine/deoxycytidine deaminase [13].
• The crystal structure of an inhibitory complex formed between Escherichia coli cytidine deaminase and the transition-state analog 3,4-dihydrouridine indicates the presence of a short H-bond between Glu-104 and the inhibitor [14].
• Cytidine deaminase (CDA) from Bacillus subtilis is a zinc-containing enzyme responsible for the hydrolytic deamination of cytidine to uridine and 2'-deoxycytidine to 2'-deoxyuridine [15].

Biological context of cdd

• The cdd-sanA (or cdd-sfiX) operon shows a highly conserved structure in E. coli and Salmonella [11].
• Fusion of the lac genes to the promotor for the cytidine deaminase gene of Escherichia coli K-12 [2].
• The structural gene that encodes cytidine deaminase (cdd) in Escherichia coli was cloned from Kohara phage lambda 365 (7F1), and its nucleotide sequence was determined [16].
• The frequency of the frameshift is approximately 16%, and it occurs both when the cdd gene is expressed from a multicopy plasmid in Escherichia coli and when it is expressed from the chromosomal copy in B. subtilis [3].
• From the results of the P1 transductions and using these Hfr strains as donors in crosses it became clear that the transcription of cir and mgl is the same and counterclockwise on the chromosome, with cdd and gat as the counterclockwise markers to mgl and cir [17].

Anatomical context of cdd

• Expression of CDD in 20 human cancer cell lines was highly variable and not related to its expression in normal tissues [5].
• Our results demonstrate that CDD can be up-regulated by vitamin D3 in some solid tumor cell lines [5].
• Northern blot analysis demonstrated high levels of CDD mRNA in leukocytes and moderate levels in liver, kidney, placenta, spleen and lung [5].

Associations of cdd with chemical compounds

• A consequence of these stereochemical differences is that in CDA a single conserved carboxylate side-chain, Glu104, can provide all of the necessary proton transfer functions involved in generating the zinc hydroxide nucleophile, and protonating the pyrimidine ring nitrogen atom and leaving amino group [18].
• Binding of pyrimidin-2-one ribonucleoside by cytidine deaminase as the transition-state analogue 3,4-dihydrouridine and the contribution of the 4-hydroxyl group to its binding affinity [12].
• Cytidine deaminase complexed to 3-deazacytidine: a "valence buffer" in zinc enzyme catalysis [19].
• Nevertheless, cytidine deaminase and mammalian plus bacterial adenosine deaminases share a single region (TVHA) of sequence identity that is tentatively identified as part of the cytidine deaminase active site [16].
• Because the hydrate is a strong inhibitor of cytidine deaminase, its use can enhance the potency of other cytosine based compounds such as 5-azacytidine (5AzaC) and cytosine arabinoside (ara-C) that are inactivated by cytidine deaminase [20].

Other interactions of cdd

• By the use of phage lambda (lac, Mu) the promoter for the cdd gene has been fused to lacZ [2].

Analytical, diagnostic and therapeutic context of cdd

• By using site-directed mutagenesis of the cdd-lacZ' fusion, it was shown that frameshifting occurred at the sequence CGA AAG, 9 bp upstream of the in-frame cdd stop codon, and that it was stimulated by a Shine-Dalgarno-like sequence located 14 bp upstream of the shift site [3].
• In the present work, we determined the thermodynamic changes associated with the equilibrium binding of inhibitors by cytidine deaminase by isothermal titration calorimetry and van't Hoff analysis of the temperature dependence of their inhibition constants [21].
• We show by sequence alignment, molecular modelling and mutagenesis, that it is related in crystal structure to the cytidine deaminase of Escherichia coli (ECCDA) [22].
• The recombinant CDA has been purified to homogeneity by a rapid procedure consisting of heat inactivation followed by affinity chromatography [23].
• The protein expressed in E. coli showed high cytidine deaminase activity and its molecular mass was estimated to be 57 kDa by gel filtration and 16 kDa by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) [23].

References