EzCatDB: S00317

DB codeS00317
RLCP classification3.133.90030.383
CATH domainDomain 13.40.50.620Catalytic domain
E.C.2.7.7.3
MACiEM0299

CATH domainRelated DB codes (homologues)
3.40.50.620S00314,S00549,S00316,S00318,S00315,T00085,T00249,D00300,M00177,M00178,T00106,T00114

Enzyme Name
Swiss-protKEGG

P0A6I6
Protein namePhosphopantetheine adenylyltransferasepantetheine-phosphate adenylyltransferase
dephospho-CoA pyrophosphorylase
pantetheine phosphate adenylyltransferase
dephospho-coenzyme A pyrophosphorylase
3'-dephospho-CoA pyrophosphorylase
SynonymsEC 2.7.7.3
Pantetheine-phosphate adenylyltransferase
PPAT
Dephospho-CoA pyrophosphorylase

KEGG pathways
MAP codePathways
MAP00770Pantothenate and CoA biosynthesis

Swiss-prot:Accession NumberP0A6I6
Entry nameCOAD_ECOLI
ActivityATP + pantetheine 4''-phosphate = diphosphate + 3''-dephospho-CoA.
SubunitHomohexamer.
Subcellular locationCytoplasm.
Cofactor


CofactorsSubstratesProducts
KEGG-idC00305C00002C01134C00013C00882
CompoundMagnesiumATPPantetheine 4'-phosphatePyrophosphateDephospho-CoA
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidecarbohydrate,peptide/protein,phosphate group/phosphate ion,sulfhydryl groupphosphate group/phosphate ionamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl group
1b6tAUnboundUnboundUnboundUnboundUnbound
1b6tBUnboundUnboundUnboundUnboundBound:COD
1qjcAUnboundUnboundUnboundUnboundUnbound
1qjcBUnboundUnboundBound:PNSUnboundUnbound
1gn8AAnalogue:_MNBound:ATPUnboundUnboundUnbound
1gn8BAnalogue:_MNBound:ATPUnboundUnboundUnbound
1h1tAUnboundUnboundUnboundUnboundAnalogue:COA
1h1tBUnboundUnboundBound:PNSUnboundUnbound

Active-site residues
resource
ATP binding site(1gn8), literature [4]
pdbCatalytic residues
1b6tAHIS 18;LYS 42;ARG 91;SER 129
1b6tBHIS 18;LYS 42;ARG 91;SER 129
1qjcAHIS 18;LYS 42;ARG 91;SER 129
1qjcBHIS 18;LYS 42;ARG 91;SER 129
1gn8AHIS 18;LYS 42;ARG 91;SER 129
1gn8BHIS 18;LYS 42;ARG 91;SER 129
1h1tAHIS 18;LYS 42;ARG 91;SER 129
1h1tBHIS 18;LYS 42;ARG 91;SER 129

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.2025-2027
[2]p.27111
[4]Fig.3, p.493-494

references
[1]
PubMed ID10205156
JournalEMBO J
Year1999
Volume18
Pages2021-30
AuthorsIzard T, Geerlof A
TitleThe crystal structure of a novel bacterial adenylyltransferase reveals half of sites reactivity.
Related PDB1b6t
Related Swiss-protP0A6I6
[2]
PubMed ID10480925
JournalJ Biol Chem
Year1999
Volume274
Pages27105-11
AuthorsGeerlof A, Lewendon A, Shaw WV
TitlePurification and characterization of phosphopantetheine adenylyltransferase from Escherichia coli.
[3]
PubMed ID10329792
JournalActa Crystallogr D Biol Crystallogr
Year1999
Volume55
Pages1226-8
AuthorsIzard T, Geerlof A, Lewendon A, Barker JJ
TitleCubic crystals of phosphopantetheine adenylyltransferase from Escherichia coli.
[4]
PubMed ID11812124
JournalJ Mol Biol
Year2002
Volume315
Pages487-95
AuthorsIzard T
TitleThe crystal structures of phosphopantetheine adenylyltransferase with bound substrates reveal the enzyme's catalytic mechanism.
Related PDB1qjc,1gn8
[5]
PubMed ID12837781
JournalJ Bacteriol
Year2003
Volume185
Pages4074-80
AuthorsIzard T
TitleA novel adenylate binding site confers phosphopantetheine adenylyltransferase interactions with coenzyme A.
Related PDB1h1t

comments
This enzyme catalyzes the transfer of an adenylyl group, whose reactive site is alpha-phosphate group, from ATP to 4'-phosphopantetheine (PPANT) in the presence of magnesium, according to the literature [4]. Here, the adenylyl group and pyrophosphate composed of beta- and gamma- phosphate of ATP are the transferred group and leaving group (donor group), respectively, whilst the 4'-phosphate of PPANT is acceptor group, in this transfer reaction.
According to the paper [4], the 4'-phosphate of PPANT makes a nucleophilic attack on the alpha-phosphate of nucleotide in an in-line displacement mechanism. During this reaction, this enzyme lowers the activation energy barrier by orienting the nucleotide and stabilizing the pentacovalent transition state.
His18 plays an essential role, by interacting with alpha-phosphate group of ATP, during the transition state stabilization. In addition, Lys42 and Thr10 orient the nucleophile, 4'-phosphate group of PPANT, whilst the sidechain of Arg91, Ser128 and Ser130 and the amide group of Ser129 stabilize the beta and gamma-phosphate group of ATP.
In the crystal structure of this enzyme, the catalytic metal ion is coordinated by the non-esterified oxygen atoms of all three phosphate groups of ATP, whilst the enzyme sidechians contributing to the coordination of the cation could not be found [4]. This result suggests that the catalytic ion might contribute to both the transferred group and leaving group (donor group) of ATP.

createdupdated
2002-05-292009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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