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

---

Query: EC:3.5.1.4 (deaminase)
5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromatography on phosphocellulose P-11 under conditions different from those applicable for deaminases specific to 5' AMP resulted in homogeneous preparation of snail foot muscle enzyme. Snail deaminase is a tetramer with molecular weight of 240,000, composed of four apparently identical subunits. Its amino acid composition is remarkably different from deaminases of higher animals, it was not inhibited by EDTA, but zinc became inhibitory to the snail enzyme. Unlike deaminases specific to 5' AMP, nonspecific deaminase is not a zinc-containing enzyme. It was adopted further for the preparation of hypoxanthine derivatives of adenosine-containing nucleotides such as NAD, NADH, AMP-P(NH)P, AMP, ADP and ATP.
...
PMID:Nonspecific snail muscle adenylate deaminase: simplified purification, characterization and use for the preparation of deamino derivatives of NAD, NADH and AMP-P(NH)P. 380 47

1. Pseudomonas sp. N.C.I.B. 8858 grew well on d- and l-1-aminopropan-2-ol and on aminoacetone. 2. Cell-free extracts possessed high activities of inducibly formed l-1-aminopropan-2-ol-NAD(+) oxidoreductase, amino alcohol-ATP phosphotransferase, dl-1-aminopropan-2-ol O-phosphate phospho-lyase and aldehyde-NAD(+) oxidoreductase, but no 1-aminopropan-2-ol racemase or d-1-aminopropan-2-ol-NAD(+) oxidoreductase. 3. The amino alcohol kinase (activated by ADP) was non-stereospecific towards 1-aminopropan-2-ol and was one-third as active with ethanolamine. The phospho-lyase was active with l- and d-1-aminopropan-2-ol O-phosphate, but ethanolamine O-phosphate was only one-tenth as active as its higher homologues. The purified aldehyde dehydrogenase was active with propionaldehyde, acetaldehyde and also with methylglyoxal. The previously observed 2-oxo aldehyde dehydrogenase activity was considered to be due to the broadly specific aldehyde dehydrogenase. 4. Mutants of Pseudomonas sp. N.C.I.B. 8858 deficient in 1-aminopropan-2-ol kinase, 1-aminopropan-2-ol O-phosphate phospho-lyase, aldehyde dehydrogenase or an enzyme involved in propionate metabolism were incapable of growth on aminoacetone or 1-aminopropan-2-ol as carbon source, although all except the kinase- or phospho-lyasedeficient mutants could use these compounds and ethanolamine as nitrogen sources. The aldehyde dehydrogenase-deficient mutants produced copious amounts of propionaldehyde and acetaldehyde during growth on the corresponding amino alcohols. 5. The path of aminoacetone metabolism in Pseudomonas sp. N.C.I.B. 8858 was concluded to involve l-1-aminopropan-2-ol, the O-phosphate ester of this compound, propionaldehyde and propionate as obligatory intermediates. d-1-Aminopropan-2-ol was metabolized by the same route as the l-isomer, gratuitously inducing formation of the stereospecific l-1-aminopropan-2-ol dehydrogenase. 6. Extracts of the pseudomonad grown with ethanolamine as the nitrogen source were devoid of 1-aminopropan-2-ol dehydrogenase, the kinase and the phospho-lyase, but exhibited cobamide coenzyme-dependent deaminase activity. Mutants deficient in kinase or phospho-lyase (deaminating) grew well on ethanolamine as the nitrogen source. Ethanolamine deaminase was inactive with, but inhibited by, 1-aminopropan-2-ol.
...
PMID:Microbial metabolism of amino alcohols. Aminoacetone metabolism via 1-aminopropan-2-ol in Pseudomonas sp. N.C.I.B. 8858. 436 43

Isolation and partial purification of AMP-deaminase from subfraction of soluble proteins of the mitochondrial fraction from rat liver is described. The enzyme preparations obtained deaminated AMP at the highest rate from pH 6.4 to 6.6. At the optimal pH value and in presence of optimal AMP concentrations the AMP-deaminase preparation was not activated by ATP or K+ and was inhibited by inorganic phosphate. Relationship was noted between both the content of protein in the enzyme preparations and length of the interval from composing the samples to monitoring the enzymatic activity and the following parameters of the AMP-deaminase: (a) shape of curves describing the rate of AMP deamination as a function of the nucleotide concentration, (b) reversible decrease in the AMP-deaminating activity after dialysis, (c) properties to deaminate, besides AMP, also some other nucleotides (ADP, NAD, FAD), (d) dynamics of inactivation of the enzyme preparations by controlled heating. The properties of the partially purified AMP-deaminase from the subfraction of rat liver soluble mitochondrial proteins were not identical with those described previously for other AMP-deaminases.
...
PMID:[Partial purification and properties of the adenylate deaminase from subfractions of soluble mitochondrial proteins of rat liver]. 728 62

Adenine dinucleotides such as beta-NAD, alpha-NAD, NADP, 3-aminopyridine adenine dinucleotide, flavin adenine dinucleotide, 3',5'-and 2',5'-adenylyladenosine mimicked the inhibitory effects of adenosine and adenine nucleotides on electrically evoked contractions of the rat and mouse isolated superfused vas deferens. The inhibitory effects were blocked by theophylline or adenosine deaminase, unaffected by the nucleotidase inhibitor alpha, beta-methylene ADP and enhanced by inhibition of adenosine deaminase. The inhibitory effects were associated with a release of purines from the vasa after preloading with [3H]adenosine. It is suggested that these compounds activate a receptor, causing the release of adenosine which is largely responsible for the inhibitions. Diadenosine pyrophosphate and triphosphate caused only depression of the vas twitch, whereas the pentaphosphate and hexaphosphate derivatives caused contraction, followed by inhibition at higher concentrations. These inhibitions were only partly reduced by theophylline or deaminase, but both contractile and inhibitory effects were enhanced by alpha, beta-methylene ADP. Noradrenaline contractions were also reduced by the higher polyphosphates. It is suggested that there may be a receptor for these dinucleotides, located at least in part postjunctionally. The pentaphosphate and hexaphosphate compounds mimicked the effects of nerve stimulation on the guinea-pig bladder, being substantially more potent than beta, gamma-methylene-ATP, and on the taenia caeci, where contraction or relaxation could be produced depending on resting tone.
...
PMID:Actions of adenine dinucleotides on the vas deferens, guinea-pig taenia caeci and bladder. 731 4

NAD synthetase catalyzes the final step in the biosynthesis of NAD. In the present study, we obtained cDNAs for two types of human NAD synthetase (referred as NADsyn1 and NADsyn2). Structural analysis revealed in both NADsyn1 and NADsyn2 a domain required for NAD synthesis from ammonia and in only NADsyn1 an additional carbon-nitrogen hydrolase domain shared with enzymes of the nitrilase family that cleave nitriles as well as amides to produce the corresponding acids and ammonia. Consistent with the domain structures, biochemical assays indicated (i) that both NADsyn1 and NADsyn2 have NAD synthetase activity, (ii) that NADsyn1 uses glutamine as well as ammonia as an amide donor, whereas NADsyn2 catalyzes only ammonia-dependent NAD synthesis, and (iii) that mutant NADsyn1 in which Cys-175 corresponding to the catalytic cysteine residue in nitrilases was replaced with Ser does not use glutamine. Kinetic studies suggested that glutamine and ammonia serve as physiological amide donors for NADsyn1 and NADsyn2, respectively. Both synthetases exerted catalytic activity in a multimeric form. In the mouse, NADsyn1 was seen to be abundantly expressed in the small intestine, liver, kidney, and testis but very weakly in the skeletal muscle and heart. In contrast, expression of NADsyn2 was observed in all tissues tested. Therefore, we conclude that humans have two types of NAD synthetase exhibiting different amide donor specificity and tissue distributions. The ammonia-dependent synthetase has not been found in eucaryotes until this study. Our results also indicate that the carbon-nitrogen hydrolase domain is the functional domain of NAD synthetase to make use of glutamine as an amide donor in NAD synthesis. Thus, glutamine-dependent NAD synthetase may be classified as a possible glutamine amidase in the nitrilase family. Our molecular identification of NAD synthetases may prove useful to learn more of mechanisms regulating cellular NAD metabolism.
...
PMID:Molecular identification of human glutamine- and ammonia-dependent NAD synthetases. Carbon-nitrogen hydrolase domain confers glutamine dependency. 1254 21

Biocatalytic processes were used to prepare chiral intermediates for pharmaceuticals. These include the following processes. Enzymatic synthesis of [4S-(4a,7a,10ab)]1-octahydro-5-oxo-4-[[(phenylmethoxy) carbonyl]amino]-7H-pyrido-[2,1-b] [1,3]thiazepine-7-carboxylic acid methyl ester (BMS-199541-01), a key chiral intermediate for synthesis of a new vasopeptidase inhibitor. Enzymatic oxidation of the epsilon-amino group of lysine in dipeptide dimer N2-[N[[(phenylmethoxy)carbonyl] L-homocysteinyl] L-lysine)1,1-disulfide (BMS-201391-01) to produce BMS-199541-01 using a novel L-lysine epsilon-aminotransferase from S. paucimobilis SC16113 was demonstrated. This enzyme was overexpressed in E. coli, and a process was developed using recombinant enzyme. The aminotransferase reaction required alpha-ketoglutarate as the amine acceptor. Glutamate formed during this reaction was recycled back to alpha-ketoglutarate by glutamate oxidase from S. noursei SC6007. Synthesis and enzymatic conversion of 2-keto-6-hydroxyhexanoic acid 5 to L-6-hydroxy norleucine 4 was demonstrated by reductive amination using beef liver glutamate dehydrogenase. To avoid the lengthy chemical synthesis of ketoacid 5, a second route was developed to prepare the ketoacid by treatment of racemic 6-hydroxy norleucine (readily available from hydrolysis of 5-(4-hydroxybutyl) hydantoin, 6) with D-amino acid oxidase from porcine kidney or T. variabilis followed by reductive amination to convert the mixture to L-6-hydroxynorleucine in 98% yield and 99% enantiomeric excess. Enzymatic synthesis of (S)-2-amino-5-(1,3-dioxolan-2-yl)-pentanoic acid (allysine ethylene acetal, 7), one of three building blocks used for synthesis of a vasopeptidase inhibitor, was demonstrated using phenylalanine dehydrogenase from T. intermedius. The reaction requires ammonia and NADH. NAD produced during the reaction was recycled to NADH by oxidation of formate to CO2 using formate dehydrogenase. Efficient synthesis of chiral intermediates required for total chemical synthesis of a beta 3 receptor agonist was demonstrated. These include: (a) microbial reduction of 4-benzyloxy-3-methanesulfonylamino-2'-bromoacetophenone 9 to corresponding (R)-alcohol 10 by S. paucimobilis SC16113, (b) enzymatic resolution of racemic alpha-methyl phenylalanine amide 11 and alpha-methyl-4-hydroxyphenylalanine amide 13 by amidase from M. neoaurum ATCC 25795 to prepare corresponding (S)-amino acids 12 and 14, and (c) asymmetric hydrolysis of methyl-(4-methoxyphenyl)-propanedioic acid ethyl diester 15 to corresponding (S)-monoester 16 by pig liver esterase. (S)[1-(acetoxyl)-4-(3-phenyl)butyl]phosphonic acid diethyl ester 21, a key chiral intermediate required for total chemical synthesis of BMS-188494 (an anticholesterol drug) was prepared by stereoselective acetylation of racemic [1-(hydroxy)-4-(3-phenyl)butyl]phosphonic acid diethyl ester 22 using G. candidum lipase. Lipase-catalyzed stereoselective acetylation of racemic 7-[N,N'-bis-(benzyloxy-carbonyl)N-(guanidinoheptanoyl)]-alpha-hydroxy-glycine 24 to corresponding S-(-)-acetate 25 was demonstrated. S-(-)-acetate 25 is a key intermediate for total chemical synthesis of (-)-15-deoxyspergualin 23, an immunosuppressive agent and antitumor antibiotic. Stereoselective microbial reduction of (1S)[3-chloro-2-oxo-1-(phenyl-methyl)propyl] carbamic acid, 1,1-dimethyl-ethyl ester 26 to corresponding chiral alcohol 27a (a key chiral intermediate for HIV protease inhibitors) was also demonstrated. Stereospecific enzymatic hydrolysis of racemic epoxide RS-1-[2',3'-dihydro benzo[b]furan-4'-yl]-1,2-oxirane 29 the corresponding R-diol 30 and unreacted chiral S-epoxide 28 was demonstrated using R. glutinis and A. niger. Dynamic resolution of racemic diol RS-1-[2',3'-dihydrobenzo[b]furan-4'-yl]-ethane-1,2-diol 32 to corresponding S-diol S-1-[2',3'-dihydrobenzo[b]furan-4'-yl]-ethane-1,2-diol 31 was demonstrated using C. boidinii and P. methanolica. Chiral (S)-epoxide 28 and (S)-diol 31 are key intermediates for a new prospective circadian modulator drug. Enzymatic resolution of racemic 2-pentanol and 2-heptanol by lipase B from Candida antarctica was demonstrated. S-(+)-2-pentanol is a key chiral intermediate required for synthesis of anti-Alzheimer's drugs.
...
PMID:Microbial/enzymatic synthesis of chiral drug intermediates. 1287 94

An organism capable of growth on pyridine was isolated from soil by enrichment culture techniques and identified as Micrococcus luteus. The organism oxidized pyridine for energy and released N contained in the pyridine ring as ammonium. The organism could not grow on mono- or disubstituted pyridinecarboxylic acids or hydroxy-, chloro-, amino-, or methylpyridines. Cell extracts of M. luteus could not degrade pyridine, 2-, 3-, or 4-hydroxypyridines or 2,3-dihydroxypyridine, regardless of added cofactors or cell particulate fraction. The organism had a NAD-linked succinate-semialdehyde dehydrogenase which was induced by pyridine. Cell extracts of M. luteus had constitutive amidase activity, and washed cells degraded formate and formamide without a lag. These data are consistent with a previously reported pathway for pyridine metabolism by species of Bacillus, Brevibacterium, and Corynebacterium. Cells of M. luteus were permeable to pyridinecarboxylic acids, monohydroxypyridines, 2,3-dihydroxypyridine, and monoamino- and methylpyridines. The results provide new evidence that the metabolism of pyridine by microorganisms does not require initial hydroxylation of the ring and that permeability barriers do not account for the extremely limited range of substrate isomers used by pyridine degraders.
...
PMID:Degradation of Pyridine by Micrococcus luteus Isolated from Soil. 1634 70

Alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) is a widespread enzyme found in many bacterial species and all currently sequenced eukaryotic organisms. It occupies a key position at the branching point of two metabolic pathways: the tryptophan to quinolinate pathway and the bacterial 2-nitrobenzoic acid degradation pathway. The activity of ACMSD determines whether the metabolites in both pathways are converted to quinolinic acid for NAD biosynthesis or to acetyl-CoA for the citric acid cycle. Here we report the first high-resolution crystal structure of ACMSD from Pseudomonas fluorescens which validates our previous predictions that this enzyme is a member of the metal-dependent amidohydrolase superfamily of the (beta/alpha)(8) TIM barrel fold. The structure of the enzyme in its native form, determined at 1.65 A resolution, reveals the precise spatial arrangement of the active site metal center and identifies a potential substrate-binding pocket. The identity of the native active site metal was determined to be Zn. Also determined was the structure of the enzyme complexed with cobalt at 2.50 A resolution. The hydrogen bonding network around the metal center suggests that Arg51 and His228 may play important roles in catalysis. The metal center configuration of PfACMSD is very similar to that of Zn-dependent adenosine deaminase and Fe-dependent cytosine deaminase, suggesting that ACMSD may share certain similarities in its catalytic mechanism with these enzymes. These data enable us to propose possible catalytic mechanisms for ACMSD which appear to be unprecedented among all currently characterized decarboxylases.
...
PMID:Crystal structure of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase: insight into the active site and catalytic mechanism of a novel decarboxylation reaction. 1693 94

As part of a research program on nucleotide metabolism in potato tubers (Solanum tuberosum L.), profiles of pyridine (nicotinamide) metabolism were examined based on the in situ metabolic fate of radio-labelled precursors and the in vitro activities of enzymes. In potato tubers, [(3)H]quinolinic acid, which is an intermediate of de novo pyridine nucleotide synthesis, and [(14)C]nicotinamide, a catabolite of NAD, were utilised for pyridine nucleotide synthesis. The in situ tracer experiments and in vitro enzyme assays suggest the operation of multiple pyridine nucleotide cycles. In addition to the previously proposed cycle consisting of seven metabolites, we found a new cycle that includes newly discovered nicotinamide riboside deaminase which is also functional in potato tubers. This cycle bypasses nicotinamide and nicotinic acid; it is NAD --> nicotinamide mononucleotide --> nicotinamide riboside --> nicotinic acid riboside --> nicotinic acid mononucleotide --> nicotinic acid adenine dinucleotide --> NAD. Degradation of the pyridine ring was extremely low in potato tubers. Nicotinic acid glucoside is formed from nicotinic acid in potato tubers. Comparative studies of [carboxyl-(14)C]nicotinic acid metabolism indicate that nicotinic acid is converted to nicotinic acid glucoside in all organs of potato plants. Trigonelline synthesis from [carboxyl-(14)C]nicotinic acid was also found. Conversion was greater in green parts of plants, such as leaves and stem, than in underground parts of potato plants. Nicotinic acid utilised for the biosynthesis of these conjugates seems to be derived not only from the pyridine nucleotide cycle, but also from the de novo synthesis of nicotinic acid mononucleotide.
...
PMID:Profiles of the biosynthesis and metabolism of pyridine nucleotides in potatoes (Solanum tuberosum L.). 1982 Sep 66

The enzyme alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) is a zinc-dependent amidohydrolase that participates in picolinic acid (PA), quinolinic acid (QA) and NAD homeostasis. Indeed, the enzyme stands at a branch point of the tryptophan to NAD pathway, and determines the final fate of the amino acid, i.e. transformation into PA, complete oxidation through the citric acid cycle, or conversion into NAD through QA synthesis. Both PA and QA are key players in a number of physiological and pathological conditions, mainly affecting the central nervous system. As their relative concentrations must be tightly controlled, modulation of ACMSD activity appears to be a promising prospect for the treatment of neurological disorders, including cerebral malaria. Here we report the 2.0 A resolution crystal structure of human ACMSD in complex with the glycolytic intermediate 1,3-dihydroxyacetonephosphate (DHAP), refined to an R-factor of 0.19. DHAP, which we discovered to be a potent enzyme inhibitor, resides in the ligand binding pocket with its phosphate moiety contacting the catalytically essential zinc ion through mediation of a solvent molecule. Arg47, Asp291 and Trp191 appear to be the key residues for DHAP recognition in human ACMSD. Ligand binding induces a significant conformational change affecting a strictly conserved Trp-Met couple, and we propose that these residues are involved in controlling ligand admission into ACMSD. Our data may be used for the design of inhibitors with potential medical interest, and suggest a regulatory link between de novo NAD biosynthesis and glycolysis.
...
PMID:The crystal structure of human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase in complex with 1,3-dihydroxyacetonephosphate suggests a regulatory link between NAD synthesis and glycolysis. 1984 66


1 2 3 Next >>

---