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pyrB  -  aspartate carbamoyltransferase

Escherichia coli O157:H7 str. Sakai

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Disease relevance of pyrB


Psychiatry related information on pyrB


High impact information on pyrB

  • These tools, when applied to our initial research on E. coli aspartate transcarbamoylase (ATCase), led to the discovery of distinct subunits for catalysis and regulation and the global conformational change in the enzyme associated with its role in regulation [7].
  • Circularly permuted polypeptide chains are being used to study the folding and assembly pathways, and the recently determined crystal structure of the active nonallosteric catalytic subunit has led to new questions regarding the activated form of ATCase [7].
  • The polar domains of the two transcarbamoylases, aspartate transcarbamoylase (ATCase) and ornithine transcarbamoylase, (OTCase) from Escherichia coli bind the common substrate carbamoyl phosphate and share extensive amino-acid sequence homology [8].
  • Under the same dissociating conditions, incubating the altered CAD with the ATCase substrate carbamoyl phosphate or the bisubstrate analogue N-phosphonacetyl-L-aspartate unexpectedly leads to the reformation of hexamers [9].
  • Alanine substitutions for the ATCase residues Asp-90 and Arg-269 were generated in a bicistronic vector that encodes a 6-histidine-tagged hamster CAD [9].

Chemical compound and disease context of pyrB


Biological context of pyrB

  • In a similar fashion, this strain can also be employed to produce exclusively the catalytic subunit of the enzyme if the plasmid only carries the pyrB gene [14].
  • Although this strain is a pyrimidine auxotroph, it will grow very slowly without pyrimidines if a plasmid containing the pyrB gene is introduced into it [14].
  • This strain has a deletion in the pyrB region of the chromosome and also carries a leaky mutation in pyrF [14].
  • The catalytic cistron (pyrB) was carried by pACYC184 and expressed from its own promoter, whereas the regulatory cistron was expressed from the lac po of pBH20 [15].
  • Based on the nucleotide sequence in the intercistronic region between orf1 and pyrB a regulatory mechanism involving transcriptional termination and antitermination is proposed to control expression of the operon [16].

Associations of pyrB with chemical compounds

  • Incubation with the other ATCase substrate, aspartate, has no effect [9].
  • The carbamoyl phosphate binding domain shows a strong structural homology with the equivalent ATCase part [17].
  • In contrast, the other domain, mainly implicated in the binding of the second substrate (ornithine for OTCase and aspartate for ATCase) is poorly conserved [17].
  • Elimination of cooperativity in aspartate transcarbamylase by nitration of a single tyrosine residue [18].
  • When r139 Lys is replaced by Met, Vmax is reduced by 50% compared to wild-type ATCase, whereas it is increased about 2-fold when r142 Glu is replaced by Asp [19].

Physical interactions of pyrB


Regulatory relationships of pyrB

  • The enzyme properties of ATCase expressed from truncated versions of the Thermus pyr gene cluster in E. coli suggest that Thermus ATCase is stabilized by DHOase and that the translation product of bbc plays a role in feedback inhibition of the ATCase-DHOase complex [2].

Other interactions of pyrB

  • These results lead to the reclassification of both enzymes: ATCase, previously considered a Class C homotrimer, now falls into Class A, whereas the DHOase is a Class 1B enzyme [20].

Analytical, diagnostic and therapeutic context of pyrB

  • Site-directed mutagenesis of pyrB, which encodes the catalytic chains of the enzyme, was used to probe the functional roles of several amino acids by making more conservative substitutions [21].
  • Sequence analysis revealed the presence of two potential promoters; transcription initiated from the promoter proximal to pyrB would produce a transcript which could direct the synthesis of a 33-amino-acid leader peptide [3].
  • Molecular cloning and subsequent DNA analysis demonstrated that the pyrB and pyrI genes are contiguous with pyrI as the distal gene in the operon [22].
  • 0. When the--SH group of each catalytic (c) chain is protected, 1 Zn2+ is released for every 4 eq of PMPS added to ATCase during titration of the 24--SH groups of regulatory (r) chains [23].
  • An aspartate transcarbamylase lacking catalytic subunit interactions. Study of conformational changes by ultraviolet absorbance and circular dichroism spectroscopy [24].


  1. Genetic characterization of the folding domains of the catalytic chains in aspartate transcarbamoylase. Jenness, D.D., Schachman, H.K. J. Biol. Chem. (1983) [Pubmed]
  2. Structure and expression of a pyrimidine gene cluster from the extreme thermophile Thermus strain ZO5. Van de Casteele, M., Chen, P., Roovers, M., Legrain, C., Glansdorff, N. J. Bacteriol. (1997) [Pubmed]
  3. Cloning, nucleotide sequence and expression of the pyrBI operon of Salmonella typhimurium LT2. Michaels, G., Kelln, R.A., Nargang, F.E. Eur. J. Biochem. (1987) [Pubmed]
  4. Molecular cloning and characterization of the pyrB gene of Lactobacillus leichmannii encoding aspartate transcarbamylase. Becker, J., Brendel, M. Biochimie (1996) [Pubmed]
  5. Molecular structure of Bacillus subtilis aspartate transcarbamoylase at 3.0 A resolution. Stevens, R.C., Reinisch, K.M., Lipscomb, W.N. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  6. The effect of pH on the cooperative behavior of aspartate transcarbamylase from Escherichia coli. Pastra-Landis, S.C., Evans, D.R., Lipscomb, W.N. J. Biol. Chem. (1978) [Pubmed]
  7. Still looking for the Ivory Tower. Schachman, H.K. Annu. Rev. Biochem. (2000) [Pubmed]
  8. Reconstruction of an enzyme by domain substitution effectively switches substrate specificity. Houghton, J.E., O'Donovan, G.A., Wild, J.R. Nature (1989) [Pubmed]
  9. Substitutions in the aspartate transcarbamoylase domain of hamster CAD disrupt oligomeric structure. Qiu, Y., Davidson, J.N. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  10. Binding of bisubstrate analog promotes large structural changes in the unregulated catalytic trimer of aspartate transcarbamoylase: implications for allosteric regulation induced cell migration. Endrizzi, J.A., Beernink, P.T., Alber, T., Schachman, H.K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  11. Interaction of tetraiodofluorescein with a modified form of aspartate transcarbamylase. Kantrowitz, E.R., Jacobsberg, L.B., Landfear, S.M., Lipscomb, W.N. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  12. Determination of ligand binding: partial and full saturation of aspartate transcarbamylase. Applicability of a filter assay to weakly binding ligands. Suter, P., Rosenbusch, J.P. J. Biol. Chem. (1976) [Pubmed]
  13. Aquifex aeolicus aspartate transcarbamoylase, an enzyme specialized for the efficient utilization of unstable carbamoyl phosphate at elevated temperature. Purcarea, C., Ahuja, A., Lu, T., Kovari, L., Guy, H.I., Evans, D.R. J. Biol. Chem. (2003) [Pubmed]
  14. Superproduction and rapid purification of Escherichia coli aspartate transcarbamylase and its catalytic subunit under extreme derepression of the pyrimidine pathway. Nowlan, S.F., Kantrowitz, E.R. J. Biol. Chem. (1985) [Pubmed]
  15. Assembly of the aspartate transcarbamoylase holoenzyme from transcriptionally independent catalytic and regulatory cistrons. Foltermann, K.F., Shanley, M.S., Wild, J.R. J. Bacteriol. (1984) [Pubmed]
  16. Molecular characterization of pyrimidine biosynthesis genes from the thermophile Bacillus caldolyticus. Ghim, S.Y., Nielsen, P., Neuhard, J. Microbiology (Reading, Engl.) (1994) [Pubmed]
  17. Crystal structure of Pseudomonas aeruginosa catabolic ornithine transcarbamoylase at 3.0-A resolution: a different oligomeric organization in the transcarbamoylase family. Villeret, V., Tricot, C., Stalon, V., Dideberg, O. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  18. Elimination of cooperativity in aspartate transcarbamylase by nitration of a single tyrosine residue. Landfear, S.M., Evans, D.R., Lipscomb, W.N. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  19. Changes in stability and allosteric properties of aspartate transcarbamoylase resulting from amino acid substitutions in the zinc-binding domain of the regulatory chains. Eisenstein, E., Markby, D.W., Schachman, H.K. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  20. Aquifex aeolicus dihydroorotase: association with aspartate transcarbamoylase switches on catalytic activity. Ahuja, A., Purcarea, C., Ebert, R., Sadecki, S., Guy, H.I., Evans, D.R. J. Biol. Chem. (2004) [Pubmed]
  21. Effect of amino acid substitutions on the catalytic and regulatory properties of aspartate transcarbamoylase. Robey, E.A., Wente, S.R., Markby, D.W., Flint, A., Yang, Y.R., Schachman, H.K. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  22. Genes encoding Escherichia coli aspartate transcarbamoylase: the pyrB-pyrI operon. Pauza, C.D., Karels, M.J., Navre, M., Schachman, H.K. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  23. Mercurial-promoted Zn2+ release from Escherichia coli aspartate transcarbamoylase. Hunt, J.B., Neece, S.H., Schachman, H.K., Ginsburg, A. J. Biol. Chem. (1984) [Pubmed]
  24. An aspartate transcarbamylase lacking catalytic subunit interactions. Study of conformational changes by ultraviolet absorbance and circular dichroism spectroscopy. Kerbiriou, D., Hervé, G. J. Biol. Chem. (1977) [Pubmed]
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