Control of pyrimidine biosynthesis in mammalian tissues. III. Multiple forms of aspartate transcarbamoylase of mouse spleen

Pyrimidine biosynthesis was active in Pseudomonas citronellolis ATCC 13674 and appeared to be regulated by pyrimidines. When wild-type cells were grown on succinate in the presence of uracil, the de novo enzyme activities were depressed while only four enzyme activities were depressed in the glucose-grown cells. On either carbon source, orotic acid-grown cells had diminished aspartate transcarbamoylase, dihydroorotase or OMP decarboxylase activity. Pyrimidine limitation of glucose-grown pyrimidine auxotrophic cells resulted in de novo enzyme activities, except for transcarbamoyolase activity, that were elevated by more than 5-fold compared to their activities in uracil-grown cells. Since pyrimidine limitation of succinate-grown mutant cells produced less enzyme derepression, catabolite repression appeared to be a factor. At the level of enzyme activity, aspartate transcarbamoylase activity in P. citronellolis was strongly inhibited by all effectors tested. Compared to the regulation of pyrimidine biosynthesis in taxonomically-related species, pyrimidine biosynthesis in P. citronellolis appeared more highly regulated.Key words: pyrimidine biosynthesis, regulation, Pseudomonas citronellolis, auxotroph, aspartate transcarbamoylase, inhibition.

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Control of pyrimidine biosynthesis in mammalian tissues. II. Glutamine-utilizing carbamoyl phosphate synthetase of various experimental tumors: distribution, purification and characterization

Biochimica et Biophysica Acta (BBA) - Enzymology ◽

10.1016/0005-2744(70)90279-2 ◽

1970 ◽

Vol 220 (3) ◽

pp. 477-490 ◽

Cited By ~ 23

Author(s):

Kazuhiko Ito ◽

Shigetada Nakanishi ◽

Masaaki Terada ◽

Masamiti Tatibana

Keyword(s):

Pyrimidine Biosynthesis ◽

Carbamoyl Phosphate Synthetase ◽

Carbamoyl Phosphate ◽

Purification And Characterization ◽

Experimental Tumors ◽

Mammalian Tissues

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Further studies on multiple forms of peptidases in mammalian tissues including intestinal mucosa from children with treated and untreated coeliac disease

Clinica Chimica Acta ◽

10.1016/0009-8981(71)90361-5 ◽

1971 ◽

Vol 31 (1) ◽

pp. 55-62 ◽

Cited By ~ 11

Author(s):

J.O. Dolly ◽

Ann Dillon ◽

M.J. Duffy ◽

P.F. Fottrell

Keyword(s):

Coeliac Disease ◽

Intestinal Mucosa ◽

Multiple Forms ◽

Mammalian Tissues

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Dihydroorotase from the HyperthermophileAquifiex aeolicusIs Activated by Stoichiometric Association with Aspartate Transcarbamoylase and Forms a One-Pot Reactor for Pyrimidine Biosynthesis†‡

Biochemistry ◽

10.1021/bi801831r ◽

2009 ◽

Vol 48 (4) ◽

pp. 766-778 ◽

Cited By ~ 29

Author(s):

Pengfei Zhang ◽

Philip D. Martin ◽

Cristina Purcarea ◽

Asmita Vaishnav ◽

Joseph S. Brunzelle ◽

...

Keyword(s):

Pyrimidine Biosynthesis ◽

Aspartate Transcarbamoylase ◽

One Pot

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Crystal structure of truncated aspartate transcarbamoylase fromPlasmodium falciparum

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x16008475 ◽

2016 ◽

Vol 72 (7) ◽

pp. 523-533 ◽

Cited By ~ 5

Author(s):

Sergey Lunev ◽

Soraya S. Bosch ◽

Fernando de Assis Batista ◽

Carsten Wrenger ◽

Matthew R. Groves

Keyword(s):

Crystal Structure ◽

Active Site ◽

Active Sites ◽

Catalytic Domain ◽

De Novo ◽

Pyrimidine Biosynthesis ◽

Aspartate Transcarbamoylase ◽

Carbamoyl Phosphate ◽

Cell Parameters ◽

High Degree

Thede novopyrimidine-biosynthesis pathway ofPlasmodium falciparumis a promising target for antimalarial drug discovery. The parasite requires a supply of purines and pyrimidines for growth and proliferation and is unable to take up pyrimidines from the host. Direct (or indirect) inhibition ofde novopyrimidine biosynthesisviadihydroorotate dehydrogenase (PfDHODH), the fourth enzyme of the pathway, has already been shown to be lethal to the parasite. In the second step of the plasmodial pyrimidine-synthesis pathway, aspartate and carbamoyl phosphate are condensed toN-carbamoyl-L-aspartate and inorganic phosphate by aspartate transcarbamoylase (PfATC). In this paper, the 2.5 Å resolution crystal structure ofPfATC is reported. The space group of thePfATC crystals was determined to be monoclinicP21, with unit-cell parametersa= 87.0,b= 103.8,c= 87.1 Å, α = 90.0, β = 117.7, γ = 90.0°. The presentedPfATC model shares a high degree of homology with the catalytic domain ofEscherichia coliATC. There is as yet no evidence of the existence of a regulatory domain inPfATC. Similarly toE. coliATC,PfATC was modelled as a homotrimer in which each of the three active sites is formed at the oligomeric interface. Each active site comprises residues from two adjacent subunits in the trimer with a high degree of evolutional conservation. Here, the activity loss owing to mutagenesis of the key active-site residues is also described.

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