Aspartate transcarbamylase

Farrington, G.K., Kumar, A., and Wedler, F.C., Design and synthesis of new transition-state analogue inhibitors of aspartate transcarbamylase, /. Med. Chem., 28, 1668, 1985. 

K D. Coffins, G. R. Stark, Aspartate Transcarbamylase Interadion With the Transition State Analogue N-(Phosphonacetyl)-L-Aspartate , J. Biol. Chem. 1971,246, 6599-6605. 

Many protein molecules are composed of more than one subunit, where each subunit is a separate polypeptide chain and can form a stable folded structure by itself. The amino acid sequences can either be identical for each subunit (as in tobacco mosaic virus protein), or similar (as in the a and )3 chains of hemoglobin), or completely different (as in aspartate transcarbamylase). The assembly of many identical subunits provides a very efficient way of constructing... 

Classic doubly wound /3 sheets Lactate dehydrogenase domain 1 Alcohol dehydrogenase domain 2 Aspartate transcarbamylase catalytic domain 2 Phosphoglycerate kinase domain 1 Tyrosyl-tRNA synthetase domain 1( )... 

Aspartate transcarbamylase catalytic domain 1 Phosphofructokinase domain 1 p-Hydroxybenzoate hydroxylase domain 1 Glucosephosphate isomerase domain 1 Glutathione peroxidase C. Miscellaneous parallel a/j3 Carboxypeptidase Thioredoxin Carbonic anhydrase Phosphofructokinase domain 2 Glucosephosphate isomerase domain 2 III. Antiparallel /3 domains... 

Aspartate transcarbamylase regulatory domains 1 and 2 Streptomyces subtilisin inhibitor Glutathione reductase domain 3 Thermolysin domain 1... 

Catalytic domain 1 doubly wound parallel fi sheet Catalytic domain 2 classic doubly wound fi sheet (Fig. 76) Aspartate transaminase see Aspartate aminotransferase Aspartate transcarbamylase (Monaco et ah, 1978), see Aspartate carbamoyltransferase... 

Fig. 93. Topology diagrams for the doubly wound and miscellaneous a/p domains illustrated in Figs. 76 through 78. Arrows represent the P strands thin connections lie behind the p sheet and fat ones above it. The darkest upper box surrounds the classic doubly wound sheets successively lighter solid boxes include domains that are progressively less like the classic topology the dotted box encloses the miscellaneous a/P structures. K = kinase P = phospho DH = dehydrogenase ATCase = aspartate transcarbamylase.

Selected entries from Methods in Enzymology [vol, page(s)] Aspartate transcarbamylase [assembly effects, 259, 624-625 buffer sensitivity, 259, 625 ligation effects, 259, 625 mutation effects, 259, 626] baseline estimation [effect on parameters, 240, 542-543, 548-549 importance of, 240, 540 polynomial interpolation, 240, 540-541,549, 567 proportional method for, 240, 541-542, 547-548, 567] baseline subtraction and partial molar heat capacity, 259, 151 changes in solvent accessible surface areas, 240, 519-520, 528 characterization of membrane phase transition, 250,... 

Topoisomerase I and II Glunosy cnramide Synlha e Thynridjtale Synthase Dihydrofotale Reductase Ribonucioolide Reductase Aspartate Transcarbamylase S AdenosylnrY6thionine Synlhase... 

Schachman, H. R., Can a simple model account for the allosteric transition of aspartate transcarbamylase J. Biol. Chem. 263, 18583, 1988. 

Carbamyl-L-aspartate is the key precursor in the biosynthesis of pyrimidines. The enzyme aspartate transcarbamylase is inhibited by several pyrimidine nucleotides, notably cytidine triphosphate, and is activated by ATP, a purine nucleotide. Thus the enzyme is under feedback regulation, and controls the relative concentration of pyrimidine and purine nucleotides. 

The examples given in the preceding pages have demonstrated that zinc in metalloenzymes may have catalytic, regulatory or structural functions. In addition there are some cases where the zinc appears to have no obvious function. Its most common role is that of catalysis, while a structural role has been demonstrated conclusively in only two cases, aspartate transcarbamylase and B. subtilis a-amylase. 

As with purines, there is indirect evidence from studies in vitro that regenerating tetrathyridia of M. corti can synthesise pyrimidines de novo (315). Furthermore, aspartate transcarbamylase, the first enzyme in the pathway, has been demonstrated in Moniezia benedini (39), while five of the six pathway enzymes have been measured in H. diminuta (326). It appears, therefore, that at least some cestodes have the capacity to synthesise pyrimidines by the biosynthetic route. Little is known of pyrimidine salvage pathways in cestodes, although the key enzyme thymidine kinase has been... 

Belkai d, M., Penverne, B., Denis, M., and Herve, G. (1987). In situ behavior of the pyrimidine pathway enzymes in Saccharomyces cerevisiae. 2. Reaction mechanism of aspartate transcarbamylase dissociated from carbamylphosphate synthetase by genetic alteration. Arch. Biochem,. Biophys., 254, 568-578. 

Souciet, J. L., Nagy, M., Le Gouar, M., Lacroute, F., and Potier, S. (1989). Organization of the yeast URA2 gene identification of a defective dihydroorotase-like domain in the multifunctional carbamoylphosphate synthetase-aspartate transcarbamylase complex. Gene, 79, 59—70. 

Royer, C.A., Tauc, P., Herve, G. and Brochon, J.-C. (1987). Ligand binding and protein dynamics a fluorescence depolarization study of aspartate transcarbamylase from Escherichia coli. Biochemistry, 26, 6472-6478. 

Animal and bacterial enzymes that utilize or synthesize carbamyl phosphate have activity with acetyl phosphate. Acyl phosphatase hydrolyzes both substrates, and maybe involved in the specific dynamic action of proteins. Ornithine and aspartic transcarbamylases also synthesize acetylornithine and acetyl aspartate. Finally, bacterial carbamate kinase and animal carbamyl phosphate synthetase utilize acetyl phosphate as well as carbamyl phosphate in the synthesis of adenosine triphosphate. The synthesis of acetyl phosphate and of formyl phosphate by carbamyl phosphate synthetases is described. The mechanism of carbon dioxide activation by animal carbamyl phosphate synthetase is reviewed on the basis of the findings concerning acetate and formate activation. 

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