Amidohydrolases of the reductive pyrimidine catabolic pathway

Schnackerz, Klaus D.; Dobritzsch, Doreen

doi:10.1016/j.bbapap.2008.01.005

Cited by 25 publications

(9 citation statements)

References 73 publications

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“…53 It is known that, in mammals, degradation of uracil and thymine leads to b-alanine and (R)-b-aminoisobutyric acid, respectively. 4,54,55 Additionally, degradation of L-valine to (S)-b-aminoisobutyric acid in mammals is recognized. 4,55 In yeasts, spermine is known to be a source of b-alanine via 3-aminopropanal.…”

Section: Origin Of B-alanine and B-aminoisobutyratementioning

confidence: 99%

Biosynthesis of natural products containing β-amino acids

2014

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Covering: up to January, 2014. We focus here on β-amino acids as components of complex natural products because the presence of β-amino acids produces structural diversity in natural products and provides characteristic architectures beyond those of ordinary α-L-amino acids, thus generating significant and unique biological functions in nature. In this review, we first survey the known bioactive β-amino acid-containing natural products including nonribosomal peptides, macrolactam polyketides, and nucleoside-β-amino acid hybrids. Next, the biosynthetic enzymes that form β-amino acids from α-amino acids and the de novo synthesis of β-amino acids are summarized. Then, the mechanisms of β-amino acid incorporation into natural products are reviewed. Because it is anticipated that the rational swapping of the β-amino acid moieties with various side chains and stereochemistries by biosynthetic engineering should lead to the creation of novel architectures and bioactive compounds, the accumulation of knowledge regarding β-amino acid-containing natural product biosynthetic machinery could have a significant impact in this field. In addition, genome mining of characteristic β-amino acid biosynthetic genes and unique β-amino acid incorporation machinery could lead to the discovery of new β-amino acid-containing natural products.

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Section: Origin Of B-alanine and B-aminoisobutyratementioning

confidence: 99%

Biosynthesis of natural products containing β-amino acids

2014

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“…Dihydropyrimidinase (DHPase, EC 3.5.2.2) is involved in the degradation of pyrimidine nucleotides and is found in many organisms, such as bacteria, animals, plants, and yeast. 4,5 It is an integral part of the pyrimidine catabolic pathway, 6 which is responsible for the regulation of the pyrimidine pool available for nucleic acid synthesis and for supplying the cell with b-alanine. Deficiency of this enzyme may cause a risk of developing severe 5-fluorouracil-associated toxicity.…”

Section: Introductionmentioning

confidence: 99%

A computational study of the reaction mechanism and stereospecificity of dihydropyrimidinase

Meelua

Wanjai

Thinkumrob

et al. 2023

Phys. Chem. Chem. Phys.

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“…Dihydropyrimidinase is a key enzyme for pyrimidine catabolism [ 1 , 2 ]. Dihydropyrimidinase catalyzes the reversible cyclization of dihydrouracil to N -carbamoyl- β -alanine in the second step of the pyrimidine degradation pathway ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Structural Basis for pH-Dependent Oligomerization of Dihydropyrimidinase fromPseudomonas aeruginosaPAO1

Cheng

Huang

2018

Bioinorganic Chemistry and Applications

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Dihydropyrimidinase, a dimetalloenzyme containing a carboxylated lysine within the active site, is a member of the cyclic amidohydrolase family, which also includes allantoinase, dihydroorotase, hydantoinase, and imidase. Unlike all known dihydropyrimidinases, which are tetrameric, pseudomonal dihydropyrimidinase forms a dimer at neutral pH. In this paper, we report the crystal structure of P. aeruginosa dihydropyrimidinase at pH 5.9 (PDB entry 5YKD). The crystals of P. aeruginosa dihydropyrimidinase belonged to space group C2221 with cell dimensions of a = 108.9, b = 155.7, and c = 235.6 Å. The structure of P. aeruginosa dihydropyrimidinase was solved at 2.17 Å resolution. An asymmetric unit of the crystal contained four crystallographically independent P. aeruginosa dihydropyrimidinase monomers. Gel filtration chromatographic analysis of purified P. aeruginosa dihydropyrimidinase revealed a mixture of dimers and tetramers at pH 5.9. Thus, P. aeruginosa dihydropyrimidinase can form a stable tetramer both in the crystalline state and in the solution. Based on sequence analysis and structural comparison of the dimer-dimer interface between P. aeruginosa dihydropyrimidinase and Thermus sp. dihydropyrimidinase, different oligomerization mechanisms are proposed.

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Amidohydrolases of the reductive pyrimidine catabolic pathway

Cited by 25 publications

References 73 publications

Biosynthesis of natural products containing β-amino acids

Biosynthesis of natural products containing β-amino acids

A computational study of the reaction mechanism and stereospecificity of dihydropyrimidinase

Structural Basis for pH-Dependent Oligomerization of Dihydropyrimidinase fromPseudomonas aeruginosaPAO1

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