6.3.4.2	A20R	mutation disrupts cytoophidium assembly	744847	
6.3.4.2	C379A	mutant enzyme is fully active with ammonia but has no glutamine-dependent activity, no inhibition by glutamate gamma-semialdehyde	648963	
6.3.4.2	C404G	inactive	-, 745736	
6.3.4.2	D107A	enzyme exhibits wild-type NH3-dependent activity and affinity for glutamine, but impaired glutamine-dependent CTP formation, affinity of the mutant enzyme for GTP is reduced 2-4fold	648962	
6.3.4.2	D149E	the single point mutation in the resistant strain L2/CPEC results in loss of CTP feedback inhibition, cells are resistant to the cytotoxic effects of cyclopentenyl cytosine	-, 648995	
6.3.4.2	D70A	mutation in the ATP binding site, mutant exhibits approximately twofold increase in the number of cells containing filaments	-, 745736	
6.3.4.2	DELTA20	deletion of the N-terminal 20 amino acids alone is sufficient to disrupt cytoophidium assembly, mutant protein forms distinct cytoplasmic structures which appear as large clusters	744847	
6.3.4.2	E103A	mutant enzyme exhibits no glutamine-dependent activity and is only partially active with NH3	648962	
6.3.4.2	E146A	mutation in the ATP binding site, mutant exhibits approximately twofold increase in the number of cells containing filaments	-, 745736	
6.3.4.2	E161K	mutation in CTP binding site, filament formation is completely disrupted and the enzyme can only form foci. Mutation decreases the affinity of the enzyme for CTP	-, 745736	
6.3.4.2	E161K	specific activity of the mutant URA7-encoded and URA8-encoded enzymes are 2fold greater when compared with the wild-type enzymes. The mutant enzymes are less sensitive to CTP product inhibition with inhibitor constants for CTP of 8.4fold- and 5.5fold greater, respectively, than those of their wild-type counterparts. Cells expressing the E161K mutant enzymes on a multicopy plasmid exhibit an increase in resistance to the pyrimidine poison and cancer therapeutic drug cyclopentenylcytosine and accumulate elevated levels of CTP when compared with cells expressing the wild-type enzymes. Cells expressing the E161K mutation in the URA7-encoded CTP synthetase exhibit an 1.5fold increase in the utilization of the Kennedy pathway for phosphatidylcholine synthesis when compared with control cells. Cells bearing the mutation also exhibit an 1.5fold increase in the synthesis of phosphatidylcholine, 1.3fold for phosphatidylethanolamine and 2fold for phosphatidate and a 1.7fold decrease in synthesis of phosphatidylserine. Cells bearing the e161K mutation exhibit an 1.6fold increase in the ratio of total neutral lipids to phospholipids, an 1.4fold increase in triacylglycerol, a 1.7fold increase in free fatty acids, an1.8fold increase in ergosterol ester and a 1.3fold decrease in diacylgylcerol when compared with control cells	648976	
6.3.4.2	E362Q	turnover number for NH4Cl-dependent GTP synthesis reaction is 1.6fold higher than wild-type value	661713	
6.3.4.2	E579A	HEK 293 cells: no effect on phosphorylation of CTPS1 by glycogen synthase kinase 3	674862	
6.3.4.2	G110A	affinity of the mutant enzyme for GTP is reduced 2-4fold, enzyme exhibits wild-type NH3-dependent activity and affinity for glutamine, but impaired glutamine-dependent CTP formation	648962	
6.3.4.2	G142A	site-directed mutagenesis, inactive mutant with both ammonia and glutamine	690817	
6.3.4.2	G143A	site-directed mutagenesis, kcat/Km for ammonia-dependent and glutamine-dependent CTP formation by mutant G143A are reduced by 22fold and 16fold, respectively, compared to the wild-type enzyme. The mutant is able to form active tetramers in the presence of ATP and UTP	690817	
6.3.4.2	G146A	site-directed mutagenesis, kcat/Km for ammonia-dependent and glutamine-dependent CTP formation by mutant G143A are reduced by 1.4fold and 1.8fold, respectively, compared to the wild-type enzyme. The mutant is able to form active tetramers in the presence of ATP and UTP	690817	
6.3.4.2	G351A	mutation increases lability of the enzyme, mutant enzyme is not overproduced because of apparent instability and proteolytic degradation	648980	
6.3.4.2	G352C	mutation increases lability of the enzyme, mutation abolishes the capacity to form the covalent glutaminyl-cysteine379 catalytic intermediate, thus preventing glutamine amide transfer function, mutant enzyme is not overproduced because of apparent instability and proteolytic degradation	648980	
6.3.4.2	G352P	mutation increases lability of the enzyme, mutation abolishes the capacity to form the covalent glutaminyl-cysteine379 catalytic intermediate, thus preventing glutamine amide transfer function, mutant enzyme is not overproduced because of apparent instability and proteolytic degradation	648980	
6.3.4.2	G360A	5fold increase in GTP-dependent activation of uncoupled glutamine hydrolysis compared to wild-type enzyme. Turnover number for NH4Cl-dependent GTP synthesis reaction is 1.2fold higher than wild-type value	661713	
6.3.4.2	G360P	mutant enzyme shows no GTP activation of the uncoupled glutaminase reaction, about 4fold lower turnover number for NH4Cl-dependent CTP synthesis reaction than wild-type enzyme	661713	
6.3.4.2	H118A	mutant enzyme exhibits no glutamine-dependent activity and is only partially active with NH3	648962	
6.3.4.2	K102A	mutant enzyme exhibits wild-type activity with respect to NH3 and glutamine	648962	
6.3.4.2	K297A	replacement of lysine 297 by alanine does not affect NH3-dependent CTP formation, relative to wild-type CTPS, but reduces kcat for the glutaminase activity 78fold	672395	
6.3.4.2	K2E	mutation disrupts cytoophidium assembly	744847	
6.3.4.2	K306A	replacement of lysine 306 by alanine reduces the rate of 2',3'-dialdehyde adenosine 5'-triphosphate-dependent inactivation (Kinact = 0.0058/sec, Ki = 3.7 mM) and reduces the apparent affinity for CTPS for both ATP and UTP by 2fold. The efficiency of K306A-catalyzed glutamine-dependent CTP formation is also reduced 2fold while near wild type activity is observed when NH3 is the substrate. These findings suggest that Lys 206 is not essential for ATP binding, but does play a role in bringing about the conformational changes that mediate interactions between ATP and UTP sites, and between the ATP-binding site and the glutamine amide transfer domain	672395	
6.3.4.2	L109A	enzyme exhibits wild-type NH3-dependent activity and affinity for glutamine, but impaired glutamine-dependent CTP formation, affinity of the mutant enzyme for GTP is reduced 2-4fold	648962	
6.3.4.2	L109A	uncoupling of the hydrolysis of gamma-glutamyl hydroxamate and nascent NH2OH production from N4-hydroxy-CTP formation is more pronounced with mutant than with wild-type enzyme	661644	
6.3.4.2	additional information	deletion of the C-terminal regulatory domain, residues Ser562-Asp591, of CTPS1 greatly increases the Vmax of the enzyme	715549	
6.3.4.2	additional information	Escherichia coli CtpS can replace the enzymatic and morphogenic functions of Caulobacter crescentus CtpS	716303	
6.3.4.2	additional information	in cytoophidium assembly, formation of heteromeric CTP synthase filaments takes place, which is disrupted by CTP synthase carrying a mutated N-terminal alanine residue. N-terminal swapping, i.e. exchange of the 20 N-terminal amino acids to the residues of human and yeast CTP synthase does not affect CTPsyn cytoophidium assembly	744847	
6.3.4.2	additional information	it can be suggested that the conformational change associated with binding ATP may be transmitted through the L10-alpha11 structural unit (residues 297-312) and thereby mediate effects on the glutaminase activity of CTPS	672395	
6.3.4.2	additional information	the ura7D/ura8D double mutant, that lacks CTP synthetase activity, shows a lethal phenotype, which can be rescued by functional expression of human CTPS1 and CTPS2 genes that encode CTP synthetase enzymes. In an ura8 mutant, CTP levels are 22% lower than in wild-type, whereas the CTP concentration in an ura7 mutant is 64% lower than in wild-type	694934	
6.3.4.2	R104A	mutant enzyme exhibits no glutamine-dependent activity and is only partially active with NH3	648962	
6.3.4.2	R105A	enzyme exhibits wild-type NH3-dependent activity and affinity for glutamine, but impaired glutamine-dependent CTP formation	648962	
6.3.4.2	R359M	mutant enzyme shows no GTP activation of the uncoupled glutaminase reaction. Turnover number for NH4Cl-dependent GTP synthesis reaction is 1.1fold higher than wild-type value	661713	
6.3.4.2	R359P	mutant enzyme shows no GTP activation of the uncoupled glutaminase reaction. Turnover number for NH4Cl-dependent GTP synthesis reaction is 1.2fold lower than wild-type value	661713	
6.3.4.2	R381M	mutation in L11 lid, 3.1fold increase in the number of cells forming filaments	745736	
6.3.4.2	R381P	mutation in L11 lid, 3.1fold increase in the number of cells forming filaments	745736	
6.3.4.2	S330A	CTP synthetase activity in cells bearing the mutant enzyme is elevated, mutation causes an elevation in the Vmax of the reaction. Mutation does not have a major effect on the oligomerization of CTP synthetase	648973	
6.3.4.2	S354A	CTP synthetase activity in extracts from cells bearing the mutant enzyme is reduced when compared with cells bearing the wild-type enzyme, decrease in Vmax of the reaction. The amount of inactive dimeric enzyme form is 98% greater compared to wild-type enzyme	648973	
6.3.4.2	S36A	CTP synthetase activity in extracts from cells bearing the mutant enzyme is reduced when compared with cells bearing the wild-type enzyme, decrease in Vmax of the reaction. The amount of inactive dimeric enzyme form is 54% greater compared to wild-type enzyme	648973	
6.3.4.2	S36A	mutation in phosphorylation site, causes an approximately twofold decrease in the frequency of filament formation	-, 745736	
6.3.4.2	S454A	CTP synthetase activity in extracts from cells bearing the mutant enzyme is reduced when compared with cells bearing the wild-type enzyme. Mutation does not have a major effect on the oligomerization of CTP synthetase	648973	
6.3.4.2	S462A/T455A	S462A and T455A mutations result in a decreased CTP synthetase 1 phosphorylation which appear to be much less than of the individual mutant enzymes S462A or T455A	674816	
6.3.4.2	S568A	2fold increase in Km value for UTP. Mutation of S568A significantly increases CTPS2 activity. The S568A mutation has a greater effect on the glutamine than ammonia-dependent activity	715549	
6.3.4.2	S571A	4fold increase in Km value for UTP	715549	
6.3.4.2	S571I	Ser-571 is the major site phosphorylated by glycogen synthase kinase 3 in intact human embryonic kidney 293 cells	674862	
6.3.4.2	S571I/S574A	phosphorylation by glycogen synthase kinase 3 does not show altered incorporation of phosphate compared with S571I alone	674862	
6.3.4.2	S571I/S574A/S575A	phosphorylation by glycogen synthase kinase 3 shows a slight decrease in the amount of phosphate incorporated into CTPS1 compared with S571I/S575A, suggesting that Ser-574 may serve as a minor secondary site for glycogen synthase kinase 3 phosphorylation	674862	
6.3.4.2	S571I/S575A	phosphorylation by glycogen synthase kinase 3 shows slightly elevated amounts of phosphate incorporated into CTPS1 compared with S571I, suggesting that without the ability to phosphorylate Ser-571 or Ser-575 in vitro, glycogen synthase kinase 3 may phosphorylate an alternative site, albeit to a much lesser extent	674862	
6.3.4.2	S574A	greatly reduces phosphorylation by glycogen synthase kinase 3	674862	
6.3.4.2	S574A/S575A	greatly reduces phosphorylation by glycogen synthase kinase 3	674862	
6.3.4.2	S575A	greatly reduces phosphorylation by glycogen synthase kinase 3. Mutation of Ser-575 prevents the phosphorylation of Ser-571, suggesting that phosphorylation of Ser-575 is necessary for priming the glycogen synthase kinase 3 phosphorylation of Ser-571	674862	
6.3.4.2	S575A	site-directed mutagenesis the mutant does not interact with peptidyl prolyl isomerase Pin1	694484	
6.3.4.2	T455A	T455A mutation causes a 78% decrease in protein kinase A phosphorylation	674886	
6.3.4.2	V349S	mutation increases lability of the enzyme	648980	
6.3.4.2	Y3E	mutation disrupts cytoophidium assembly	744847