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UNG is a member of the Uracil-DNA glycosylase family. One of his functions is to prevent mutagenesis by eliminating uracil from DNAmolecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil basesare formed as a result of cytosine deamination or misincorporation of dUMP residues. After a mutation is formed, the mutagenicthreat of uracil propagates through any subsequent DNA replication steps. Among the diseases associated with UNG are: congenital rubella, and immunodeficiency with hyper igm type 4.

Uracil DNA glycosylase (UDG), or uracil-DNA glycosylase 1, is a crucial enzyme found in all life forms, involved in repairing damaged DNA by specifically removing uracil bases that are misincorporated into DNA during replication or deaminated cytosine. In various organisms, UDG goes by different names, such as b2580, JW2564, EC 3.2.2.27, DGU, UNG15, HIGM5, EC 3.2.2, HIGM4, and UNG2. Here, we delve into the E. coli UDG, examining its structure, function, and applications in molecular biology.

Structure: The crystal structure of E. coli UDG has been extensively studied, revealing that it belongs to the uracil DNA glycosylase (UDG) superfamily. The E. coli UDG monomer has 229 amino acids with a molecular weight of 25 kDa. The protein has a beta-sheet-rich structure with an alpha-helix on one side and a groove on the other side that binds to DNA. The active site of E. coli UDG contains a conserved glutamic acid residue that acts as a catalytic base to facilitate the hydrolysis of the N-glycosidic bond between uracil and the sugar phosphate backbone.

Function: E. coli UDG plays a critical role in maintaining the integrity of the genome by preventing the accumulation of mutations that can arise from the incorporation of uracil into DNA. Uracil in DNA can occur spontaneously from the deamination of cytosine or can be incorporated during DNA synthesis when dUTP is used instead of dTTP. Unrepaired uracil bases can lead to DNA damage and genomic instability, possibly resulting in cell death or disease. E. coli UDG specifically recognizes and removes uracil bases from DNA, creating an abasic site that is further processed by other repair enzymes.

AnsA is a cytoplasmic asparaginase from E.coli involved in intracellular asparagine utilization. E.coli has 2 L-asparaginases: the cytoplasmic type I form (ansA) and the periplasmic type II form (ansB). AnsA (Type L asparaginase) is constitutively expressed and is obligatory for the growth of the bacteria on asparagine as the sole nitrogen source.

N-acetylneuraminate lyase (NanA) is a member of a family of lyases, specifically the oxo-acid-lyases, which cleave carbon-carbon bonds. NanA catalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetyl-D-mannosamine. NanA is inhibited by reduction with NaBH4 in the presence of the substrate, which indicates that it belongs to the Schiff-base-forming Class I aldolases. NanA is strongly inhibited by Cu2+ ions, p-chloromercuribenzoate and N-bromosuccinimide, it is also inhibited competitively by the reaction product, pyruvate, and its structurally related compounds, dihydroxyacetone and DL-glyceraldehyde.

CBR4 is a member of the short-chain dehydrogenase/reductase family. CBR4 has a role in biosynthesis of fatty acids in the mitochondria and a broad substrate specificity and reduces 9,10-phenanthrenequinone, 1,4-benzoquinone and a range of other o-quinones and p-quinones (in vitro). CBR4 formation of a heteroteramer with HSD17B8 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity for o- and p-quinones.

UPP1 catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate which are used as carbon and energy sources or in the release of pyrimidine bases for nucleotide synthesis. UPP1 is part of the family of glycosyltransferases, specifically the pentosyltransferases. Pyrimidine nucleoside phosphorylases add ribose or deoxyribose to pyrimidine bases to form nucleosides that can be incorporated into RNA or DNA.

Glutamate Decarboxylase 2 (GAD2) is one of several forms of glutamic acid decarboxylase, identified as a main autoantigen in type II diabetes. The GAD2 enzyme is responsible for catalyzing the production of gamma-aminobutyric acid from L-glutamic acid. A pathogenic role for the GAD2 enzyme has been characterized in the human pancreas since it has been identified as an autoantibody and an autoreactive T cell target in type II diabetes. GAD2 gene may also have a role in the stiff man syndrome. In addition, GAD2 catalyzes the production of GABA.

ECHS1 is part of the hydratase/isomerase superfamily. ECHS1 is localized in the mitochondrial matrix and Expressed in muscle, liver and fibroblasts, with low expression in kidney and spleen, ECHS1 exists as a homohexamer that takes part in the second phase of the mitochondrial fatty acid β-oxidation pathway.

melA is a member of the glycosyl hydrolase 4 family. melA catalyze the hydrolysis of saccharides containing o-1,6,-galactoside bonds. melA catalyze the same reaction in E.coli, human and yeast but is found in different cellular sections: The E.coli melA is a cytoplasmic protein and the human and yeast melA are secretory proteins. Thus, even though the active enzyme from all three species has almost an equal molecular weight, structural resemblances, as well as dissimilarities, are probable.

Enoyl CoA hydratase domain containing 1 (ECHDC1) is a member of the enoyl-CoA hydratase/isomerase family. ECHDC1 is an enzyme which hydrates the double bond between the second and third carbons on acyl-CoA. The ECHDC1 enzyme is crucial to metabolizing fatty acids to supply both acetyl CoA and energy.

COAA is a member of the prokaryotic pantothenate kinase family and it is the first enzyme in the Coenzyme A biosynthetic pathway. COAA phosphorylates pantothenate (vitamin B5) to form 4'-phosphopantothenate. The key factor controlling the intracellular CoA concentration is the regulation of COAA activity by feedback inhibition.

2-Enoyl-Coenzyme A (CoA) Hydratase, Beta (HADHB) is the beta subunit of the mitochondrial trifunctional protein, that catalyzes the last 3 phases of mitochondrial beta-oxidation of long chain fatty acids. HADHB binds RNA and reduces the stability of various mRNAs. Mutations in HADHB cause trifunctional protein deficiency.

Carboxypeptidase B (EC 3.4.17.2) catalyzes hydrolysis of the basic amino acids lysine, arginine and ornithine from the C-terminal end of polypeptides. The Mw was found to be 34.5 kDa, optimun pH-7.9, and pI-6. Carboxypeptidase B is inhibited by arginine, lysine and ornithine. The enzyme is not inhibited by di-isopropylfluorophosphate (DFP), but it is inhibited by metal chelating agents, e.g., EDTA, 1,10-phenanthroline.

Thermosensitive Gluconokinase, also known as IDNK is a 187 a.a protein which is a member of the gluconokinase gntK/gntV family. IDNK catalyzes theconversion of ATP and D-gluconate to ADP and 6-phospho-D-gluconate. In addition, IDNK is considered to take part in gender determination, deletion of the distal portion of 9p is able to lead to a development of male to female sex reversal, the phenotype of a female with a male X, Y genotype.

PCBD1 enzyme takes part in phenylalanine hydroxylation. PCBD1 deficiency results in hyperphenylalaninemia. PCBD1 enzyme controls the homodimerization of HNF1. PCBD1 takes part in tetrahydrobiopterin biosynthesis. PCBD1 prevents the formation of 7-pterins and accelerate the formation of quinonoid-BH2. PCBD1 is a coactivator for HNF1A-dependent transcription.

Procollagen C-endopeptidase enhancer 1, also known as PCOLCE binds to the C-terminal propeptide of type I procollagen and enhances procollagen C-proteinase activity. In addition, C-terminal processed part of PCPE (CT-PCPE) has a metalloproteinase inhibitory activity. Among the diseases which are associated with PCOLCE: bone fracture & oculopharyngeal muscular dystrophy.

Carboxymethylenebutenolidase homolog (CMBL) is a cysteine hydrolase of the dienelactone hydrolase family which is highly expressed in the liver cytosol. CMBL is the human homolog of Pseudomonas dienelactone hydrolase, which is a protein that participates in the bacterial halocatechol degradation pathway. CMBL which preferentially cleaves cyclic esters activates medoxomil-ester prodrugs in which the medoxomil moiety is coupled with an oxygen atom. CMBL is inhibited by PCMB (p-chloromercuribenzoate) and is encoded by a gene which maps to human chromosome 5p15.2. CMBL can also activate beta-lactam antibiotics faropenem medoxomil and lenampicillin. CMBL is widely expressed, with the highest levels in the liver, followed by the kidney, small intestine and the colon.

Paraoxonase-1 or PON1 is part of the paraoxonase group of proteins. PON1 is an enzyme, responsible to the toxic metabolites of a different of organophosphorus insecticides hydrolyzation. Furthermore, PON1 is a dominant anti-atherosclerotic part of HDL. The enzyme needs PPAR-gamma for activation, leading to synthesis and release of paraoxonase 1 from the liver tissue, resulting in atherosclerosis reduction. PON1 has many qualities for atheroprotective through inflammatory lipid peroxides metabolism. This enzyme can hydrolyze a large number of substrates, for example cyclic carbonates, lactones, nerve gases etc.

CBR3 catalyzes the reduction of a large number of biologically and pharmacologically active carbonyl compounds to their corresponding alcohols. CBR3 is one of several monomeric NADPH-dependent oxidoreductases. Furthermore, CBR3 contains 3 exons spanning 11.2 kilobases and is strongly linked to another carbonyl reductase gene, the CBR1. It was suggested that CBR3 mediates 9-cis-retinoic acid-induced cytostatis and is a potential prognostic marker for oral malignancy. CBR3 is identified in the ovary, pancreas, intestine, colon, kidney, brain, thymus, lung, heart, liver, spleen, leukocyte, prostate and the testis. Polymorphisms in CBR3 may give an explanation to interindividual and interethnic variability of doxorubicin pharmacokinetics and pharmacodynamics.

Endonuclease III (nth) is a DNA repair enzyme which has both DNA N-glycosylase activity and AP-lyase activity. The DNA N-glycosylase activity releases numerous damaged pyrimidines from DNA by cleaving the N-glycosidic bond and leaving an AP (apurinic/apyrimidinic) site. This AP-lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination, thus leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.

MMAB protein catalyzes the last step in the conversion of vitamin B(12) into adenosylcobalamin (AdoCbl), a vitamin B12 containing coenzyme for methylmalonyl-CoA mutase(MCM). Decreased MMAB activity leads to the inherited disorder vitamin B12 dependent methylmalonic aciduria linked to the cblB complementation group.

Dehydrogenase/reductase SDR family member 4 (DHRS4) is a member of the short-chain dehydrogenases/reductases (SDR) family. DHRS4 reduces all trans retinal and 9-cis retinal. In addition, the DHRS4 protein can catalyze the oxidation of all trans retinol with NADP as cofactor, but with a much lower efficiency. Furthermore, DHRS4 reduces alkyl phenyl ketones and alpha dicarbonyl compounds with aromatic rings, such as pyrimidine 4 aldehyde, 3 benzoylpyridine, 4 benzoylpyridine, menadione and 4 hexanoylpyridine.

Aldo-keto reductase family 1 member C3 isoform 1 or AKR1C3 is an enzyme, part of the aldo-keto reductase family that promotes conversion of ketones & aldehydes to the alcohol forms while using cofactors such as NADPH & NADH. AKR1C3 promotes the reduction of PG molecule (prostaglandin), PQ (phenanthrenequinone) & PGH2. Another role is oxidation of 9 alpha, 11 beta-PGF2 to PGD2. AKR1C3 holds a crucial part in the pathogenesis of allergic diseases like asthma and can also take part in the regulation of cell growth and differentiation.

Acetyl-COA Acyltransferase 2, (ACAA2) is a member of the thiolase family. ACAA2 catalyzes the final step of the mitochondrial fatty acid beta-oxidation spiral. Not like most mitochondrial matrix proteins, ACAA2 contains a non-cleavable amino-terminal targeting signal.