DB code: S00317

RLCP classification 3.133.90030.383 : Transfer
CATH domain 3.40.50.620 : Rossmann fold Catalytic domain
E.C. 2.7.7.3
CSA
M-CSA
MACiE M0299

CATH domain Related DB codes (homologues)
3.40.50.620 : Rossmann fold S00314 S00549 S00316 S00318 S00315 T00085 T00249 D00300 M00177 M00178 T00106 T00114

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P0A6I6 Phosphopantetheine adenylyltransferase
EC 2.7.7.3
Pantetheine-phosphate adenylyltransferase
PPAT
Dephospho-CoA pyrophosphorylase
NP_418091.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_491799.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF01467 (CTP_transf_2)
[Graphical View]

KEGG enzyme name
pantetheine-phosphate adenylyltransferase
dephospho-CoA pyrophosphorylase
pantetheine phosphate adenylyltransferase
dephospho-coenzyme A pyrophosphorylase
3'-dephospho-CoA pyrophosphorylase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0A6I6 COAD_ECOLI ATP + pantetheine 4''-phosphate = diphosphate + 3''-dephospho-CoA. Homohexamer. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00770 Pantothenate and CoA biosynthesis

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C01134 C00013 C00882
E.C.
Compound Magnesium ATP Pantetheine 4'-phosphate Pyrophosphate Dephospho-CoA
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide carbohydrate,peptide/protein,phosphate group/phosphate ion,sulfhydryl group phosphate group/phosphate ion amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group
ChEBI 18420
15422
4222
29888
15468
PubChem 888
5957
115254
1023
21961011
444485
1b6tA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1b6tB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:COD
1qjcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qjcB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:PNS Unbound Unbound
1gn8A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_MN Bound:ATP Unbound Unbound Unbound
1gn8B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_MN Bound:ATP Unbound Unbound Unbound
1h1tA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:COA
1h1tB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:PNS Unbound Unbound

Reference for Active-site residues
resource references E.C.
ATP binding site(1gn8), literature [4]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1b6tA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 18;LYS 42;ARG 91;SER 129
1b6tB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 18;LYS 42;ARG 91;SER 129
1qjcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 18;LYS 42;ARG 91;SER 129
1qjcB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 18;LYS 42;ARG 91;SER 129
1gn8A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 18;LYS 42;ARG 91;SER 129
1gn8B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 18;LYS 42;ARG 91;SER 129
1h1tA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 18;LYS 42;ARG 91;SER 129
1h1tB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 18;LYS 42;ARG 91;SER 129

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.2025-2027
[2]
p.27111
[4]
Fig.3, p.493-494

References
[1]
Resource
Comments
Medline ID
PubMed ID 10205156
Journal EMBO J
Year 1999
Volume 18
Pages 2021-30
Authors Izard T, Geerlof A
Title The crystal structure of a novel bacterial adenylyltransferase reveals half of sites reactivity.
Related PDB 1b6t
Related UniProtKB P0A6I6
[2]
Resource
Comments
Medline ID
PubMed ID 10480925
Journal J Biol Chem
Year 1999
Volume 274
Pages 27105-11
Authors Geerlof A, Lewendon A, Shaw WV
Title Purification and characterization of phosphopantetheine adenylyltransferase from Escherichia coli.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 10329792
Journal Acta Crystallogr D Biol Crystallogr
Year 1999
Volume 55
Pages 1226-8
Authors Izard T, Geerlof A, Lewendon A, Barker JJ
Title Cubic crystals of phosphopantetheine adenylyltransferase from Escherichia coli.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 11812124
Journal J Mol Biol
Year 2002
Volume 315
Pages 487-95
Authors Izard T
Title The crystal structures of phosphopantetheine adenylyltransferase with bound substrates reveal the enzyme's catalytic mechanism.
Related PDB 1qjc 1gn8
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 12837781
Journal J Bacteriol
Year 2003
Volume 185
Pages 4074-80
Authors Izard T
Title A novel adenylate binding site confers phosphopantetheine adenylyltransferase interactions with coenzyme A.
Related PDB 1h1t
Related UniProtKB

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.

Created Updated
2002-05-29 2009-02-26