UniProt functional annotation for P0A6I6



	UniProt functional annotation for P0A6I6

UniProt code: P0A6I6.

Organism: Escherichia coli (strain K12).

Taxonomy: Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.

Function: Reversibly transfers an adenylyl group from ATP to 4'- phosphopantetheine, yielding dephospho-CoA (dPCoA) and pyrophosphate (PubMed:10480925, PubMed:17873050). CoA is not a substrate for the enzyme (PubMed:10480925). {ECO:0000255|HAMAP-Rule:MF_00151, ECO:0000269|PubMed:10480925, ECO:0000269|PubMed:17873050}.

Catalytic activity: Reaction=ATP + D-pantetheine 4'-phosphate + H(+) = 3'-dephospho-CoA + diphosphate; Xref=Rhea:RHEA:19801, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57328, ChEBI:CHEBI:61723; EC=2.7.7.3; Evidence={ECO:0000255|HAMAP- Rule:MF_00151, ECO:0000269|PubMed:10480925, ECO:0000269|PubMed:17873050};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:11812124}; Note=Crystallized in the absence of Mg(2+), the catalytic metal is not bound by the protein but probably by non-esterified oxygen atoms from ATP and/or ordered H(2)O (PubMed:11812124). {ECO:0000305|PubMed:11812124};

Activity regulation: Feedback inhibited by CoA, which is competitive with ATP, 4'-phosphopantetheine and 3'-dephospho-CoA (PubMed:17873050, PubMed:10480925). Binds 0.5 CoA tightly per monomer in the same position as 3'-dephospho-CoA but in a different fashion (PubMed:12837781, PubMed:17873050). Is inhibited by the very potent and specific inhibitor PTX042695 dipeptide, with an IC(50) of 6 nM, a compound which has no activity against porcine PPAT (PubMed:12750020). A series of pyrazoloquinolones were also characterized as ATP- competitive inhibitors of PPAT (PubMed:20486930). {ECO:0000269|PubMed:12750020, ECO:0000269|PubMed:12837781, ECO:0000269|PubMed:17873050, ECO:0000269|PubMed:20486930, ECO:0000305|PubMed:10480925}.

Biophysicochemical properties: Kinetic parameters: KM=7.0 uM for 3'-dephospho-CoA {ECO:0000269|PubMed:10480925}; KM=17.0 uM for 3'-dephospho-CoA {ECO:0000269|PubMed:17873050}; KM=0.22 mM for diphosphate {ECO:0000269|PubMed:10480925}; KM=0.23 mM for diphosphate {ECO:0000269|PubMed:17873050}; KM=220 uM for ATP {ECO:0000269|PubMed:17873050}; KM=4.7 uM for 4'-phosphopantetheine {ECO:0000269|PubMed:17873050}; Note=kcat is 1.37 sec(-1) for the forward reaction, with ATP and pantetheine 4'-phosphate as substrates (PubMed:17873050). kcat is 3.3 sec(-1) for the reverse reaction, with diphosphate and 3'-dephospho- CoA as substrates (PubMed:10480925). kcat is 1.37 sec(-1) for the reverse reaction, with diphosphate and 3'-dephospho-CoA as substrates (PubMed:17873050). {ECO:0000269|PubMed:10480925, ECO:0000269|PubMed:17873050}; pH dependence: Optimum pH is 6.9. {ECO:0000269|PubMed:10480925};

Pathway: Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)- pantothenate: step 4/5. {ECO:0000255|HAMAP-Rule:MF_00151}.

Subunit: Homohexamer, a dimerized trimer with a solvent channel through the middle (PubMed:10480925, PubMed:10205156, PubMed:11812124, PubMed:12837781, PubMed:17873050). In crystals only 1 trimer is seen to bind substrate/product at a time (PubMed:10205156, PubMed:11812124). {ECO:0000269|PubMed:10205156, ECO:0000269|PubMed:10480925, ECO:0000269|PubMed:11812124, ECO:0000269|PubMed:12837781, ECO:0000269|PubMed:17873050}.

Subcellular location: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00151}.

Miscellaneous: The crystal structures in complex with substrates suggest the enzyme stabilizes the transition state but the functional groups of the enzyme are not directly involved in reaction catalysis. {ECO:0000305|PubMed:11812124}.

Similarity: Belongs to the bacterial CoaD family. {ECO:0000255|HAMAP- Rule:MF_00151}.

Annotations taken from UniProtKB at the EBI.


Organism:		Escherichia coli (strain K12).
Taxonomy:		Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.



Function:		Reversibly transfers an adenylyl group from ATP to 4'- phosphopantetheine, yielding dephospho-CoA (dPCoA) and pyrophosphate (PubMed:10480925, PubMed:17873050). CoA is not a substrate for the enzyme (PubMed:10480925). {ECO:0000255\|HAMAP-Rule:MF_00151, ECO:0000269\|PubMed:10480925, ECO:0000269\|PubMed:17873050}.


Catalytic activity:		Reaction=ATP + D-pantetheine 4'-phosphate + H(+) = 3'-dephospho-CoA + diphosphate; Xref=Rhea:RHEA:19801, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57328, ChEBI:CHEBI:61723; EC=2.7.7.3; Evidence={ECO:0000255\|HAMAP- Rule:MF_00151, ECO:0000269\|PubMed:10480925, ECO:0000269\|PubMed:17873050};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:11812124}; Note=Crystallized in the absence of Mg(2+), the catalytic metal is not bound by the protein but probably by non-esterified oxygen atoms from ATP and/or ordered H(2)O (PubMed:11812124). {ECO:0000305\|PubMed:11812124};
Activity regulation:		Feedback inhibited by CoA, which is competitive with ATP, 4'-phosphopantetheine and 3'-dephospho-CoA (PubMed:17873050, PubMed:10480925). Binds 0.5 CoA tightly per monomer in the same position as 3'-dephospho-CoA but in a different fashion (PubMed:12837781, PubMed:17873050). Is inhibited by the very potent and specific inhibitor PTX042695 dipeptide, with an IC(50) of 6 nM, a compound which has no activity against porcine PPAT (PubMed:12750020). A series of pyrazoloquinolones were also characterized as ATP- competitive inhibitors of PPAT (PubMed:20486930). {ECO:0000269\|PubMed:12750020, ECO:0000269\|PubMed:12837781, ECO:0000269\|PubMed:17873050, ECO:0000269\|PubMed:20486930, ECO:0000305\|PubMed:10480925}.
Biophysicochemical properties:		Kinetic parameters: KM=7.0 uM for 3'-dephospho-CoA {ECO:0000269\|PubMed:10480925}; KM=17.0 uM for 3'-dephospho-CoA {ECO:0000269\|PubMed:17873050}; KM=0.22 mM for diphosphate {ECO:0000269\|PubMed:10480925}; KM=0.23 mM for diphosphate {ECO:0000269\|PubMed:17873050}; KM=220 uM for ATP {ECO:0000269\|PubMed:17873050}; KM=4.7 uM for 4'-phosphopantetheine {ECO:0000269\|PubMed:17873050}; Note=kcat is 1.37 sec(-1) for the forward reaction, with ATP and pantetheine 4'-phosphate as substrates (PubMed:17873050). kcat is 3.3 sec(-1) for the reverse reaction, with diphosphate and 3'-dephospho- CoA as substrates (PubMed:10480925). kcat is 1.37 sec(-1) for the reverse reaction, with diphosphate and 3'-dephospho-CoA as substrates (PubMed:17873050). {ECO:0000269\|PubMed:10480925, ECO:0000269\|PubMed:17873050}; pH dependence: Optimum pH is 6.9. {ECO:0000269\|PubMed:10480925};
Pathway:		Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)- pantothenate: step 4/5. {ECO:0000255\|HAMAP-Rule:MF_00151}.
Subunit:		Homohexamer, a dimerized trimer with a solvent channel through the middle (PubMed:10480925, PubMed:10205156, PubMed:11812124, PubMed:12837781, PubMed:17873050). In crystals only 1 trimer is seen to bind substrate/product at a time (PubMed:10205156, PubMed:11812124). {ECO:0000269\|PubMed:10205156, ECO:0000269\|PubMed:10480925, ECO:0000269\|PubMed:11812124, ECO:0000269\|PubMed:12837781, ECO:0000269\|PubMed:17873050}.
Subcellular location:		Cytoplasm {ECO:0000255\|HAMAP-Rule:MF_00151}.
Miscellaneous:		The crystal structures in complex with substrates suggest the enzyme stabilizes the transition state but the functional groups of the enzyme are not directly involved in reaction catalysis. {ECO:0000305\|PubMed:11812124}.
Similarity:		Belongs to the bacterial CoaD family. {ECO:0000255\|HAMAP- Rule:MF_00151}.