PDBsum entry 1qjc

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Coenzyme a biosynthesis PDB id
Protein chains
157 a.a. *
SO4 ×5
Waters ×277
* Residue conservation analysis
PDB id:
Name: Coenzyme a biosynthesis
Title: Phosphopantetheine adenylytransferase from escherichia coli in complex with 4'-phosphopantetheine
Structure: Phosphopantetheine adenylyltransferase. Chain: a, b. Synonym: ppat, pantetheine-phosphate adenylyltransferase, dephospho-coa pyrophosphorylase. Ec:
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Hexamer (from PDB file)
1.64Å     R-factor:   0.216     R-free:   0.247
Authors: T.Izard
Key ref:
T.Izard (2002). The crystal structures of phosphopantetheine adenylyltransferase with bound substrates reveal the enzyme's catalytic mechanism. J Mol Biol, 315, 487-495. PubMed id: 11812124 DOI: 10.1006/jmbi.2001.5272
23-Jun-99     Release date:   27-Jun-01    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0A6I6  (COAD_ECOLI) -  Phosphopantetheine adenylyltransferase
159 a.a.
157 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Pantetheine-phosphate adenylyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Coenzyme A Biosynthesis (late stages)
      Reaction: ATP + pantetheine 4'-phosphate = diphosphate + 3'-dephospho-CoA
pantetheine 4'-phosphate
Bound ligand (Het Group name = PNS)
corresponds exactly
= diphosphate
+ 3'-dephospho-CoA
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     biosynthetic process   2 terms 
  Biochemical function     catalytic activity     6 terms  


DOI no: 10.1006/jmbi.2001.5272 J Mol Biol 315:487-495 (2002)
PubMed id: 11812124  
The crystal structures of phosphopantetheine adenylyltransferase with bound substrates reveal the enzyme's catalytic mechanism.
Phosphopantetheine adenylyltransferase (PPAT) is an essential enzyme in the coenzyme A pathway that catalyzes the reversible transfer of an adenylyl group from ATP to 4'-phosphopantetheine (Ppant) in the presence of magnesium. To investigate the reaction mechanism, the high-resolution crystal structures of the Escherichia coli PPAT have been determined in the presence of either ATP or Ppant. Structural details of the catalytic center revealed specific roles for individual amino acid residues involved in substrate binding and catalysis. The side-chain of His18 stabilizes the expected pentacovalent intermediate, whereas the side-chains of Thr10 and Lys42 orient the nucleophile for an in-line displacement mechanism. The binding site for the manganese ion that interacts with the phosphate groups of the nucleotide has also been identified. Within the PPAT hexamer, one trimer is in its substrate-free state, whereas the other is in a substrate-bound state.
  Selected figure(s)  
Figure 1.
Figure 1. Stereodiagram of the PPAT dimer within the asymmetric unit looking down the non-crystallographic dyad. The unliganded protomer is colored in light blue and the liganded protomer in pink. The ligands (Ppant from the PPAT:Ppant structure, Mn2+-ATP from the PPAT:ATP structure, and sulfate anions found in all PPAT structures) are shown in ball-and-stick representation. Oxygen atoms are red; nitrogen, blue; sulfur, green; carbon, yellow; phosphate, black; and manganese, gray. This Figure and Figure 2 were produced with MOLSCRIPT or BobScript [25] and Raster3D. [26]
Figure 3.
Figure 3. Interaction of the attacking nucleophile and phosphate group that might occur in an in-line displacement mechanism during the PPAT reaction. Ppant is shown in red, Mg2+-ATP in blue, and PPAT in black. The hydrogen-bonding network of the proposed catalytic residues to the substrates is indicated and the distances (Å) between the two electronegative atoms are given.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 315, 487-495) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21527250 C.S.Cheng, C.H.Chen, Y.C.Luo, W.T.Chen, S.Y.Chang, P.C.Lyu, M.C.Kao, and H.S.Yin (2011).
Crystal structure and biophysical characterisation of Helicobacter pylori phosphopantetheine adenylyltransferase.
  Biochem Biophys Res Commun, 408, 356-361.  
21070951 B.H.Dessailly, O.C.Redfern, A.L.Cuff, and C.A.Orengo (2010).
Detailed analysis of function divergence in a large and diverse domain superfamily: toward a refined protocol of function classification.
  Structure, 18, 1522-1535.  
20486930 J.R.Miller, V.Thanabal, M.M.Melnick, M.Lall, C.Donovan, R.W.Sarver, D.Y.Lee, J.Ohren, and D.Emerson (2010).
The use of biochemical and biophysical tools for triage of high-throughput screening hits - A case study with Escherichia coli phosphopantetheine adenylyltransferase.
  Chem Biol Drug Des, 75, 444-454.  
19783652 J.Lee, J.Johnson, Z.Ding, M.Paetzel, and R.B.Cornell (2009).
Crystal structure of a mammalian CTP: phosphocholine cytidylyltransferase catalytic domain reveals novel active site residues within a highly conserved nucleotidyltransferase fold.
  J Biol Chem, 284, 33535-33548.
PDB code: 3hl4
19136717 S.Frago, A.Velázquez-Campoy, and M.Medina (2009).
The Puzzle of Ligand Binding to Corynebacterium ammoniagenes FAD Synthetase.
  J Biol Chem, 284, 6610-6619.  
18811972 S.Frago, M.Martínez-Júlvez, A.Serrano, and M.Medina (2008).
Structural analysis of FAD synthetase from Corynebacterium ammoniagenes.
  BMC Microbiol, 8, 160.  
17873050 J.R.Miller, J.Ohren, R.W.Sarver, W.T.Mueller, Dreu, H.Case, and V.Thanabal (2007).
Phosphopantetheine adenylyltransferase from Escherichia coli: investigation of the kinetic mechanism and role in regulation of coenzyme A biosynthesis.
  J Bacteriol, 189, 8196-8205.  
  17077496 J.Y.Kang, H.H.Lee, H.J.Yoon, H.S.Kim, and S.W.Suh (2006).
Overexpression, crystallization and preliminary X-ray crystallographic analysis of phosphopantetheine adenylyltransferase from Enterococcus faecalis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1131-1133.  
16648134 Y.M.Zhang, S.W.White, and C.O.Rock (2006).
Inhibiting bacterial fatty acid synthesis.
  J Biol Chem, 281, 17541-17544.  
14684898 H.Takahashi, E.Inagaki, Y.Fujimoto, C.Kuroishi, Y.Nodake, Y.Nakamura, F.Arisaka, K.Yutani, S.Kuramitsu, S.Yokoyama, M.Yamamoto, M.Miyano, and T.H.Tahirov (2004).
Structure and implications for the thermal stability of phosphopantetheine adenylyltransferase from Thermus thermophilus.
  Acta Crystallogr D Biol Crystallogr, 60, 97.
PDB code: 1od6
15322293 V.K.Morris, and T.Izard (2004).
Substrate-induced asymmetry and channel closure revealed by the apoenzyme structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase.
  Protein Sci, 13, 2547-2552.
PDB code: 1tfu
12756245 J.Armengaud, B.Fernandez, V.Chaumont, F.Rollin-Genetet, S.Finet, C.Marchetti, H.Myllykallio, C.Vidaud, J.L.Pellequer, S.Gribaldo, P.Forterre, and P.Gans (2003).
Identification, purification, and characterization of an eukaryotic-like phosphopantetheine adenylyltransferase (coenzyme A biosynthetic pathway) in the hyperthermophilic archaeon Pyrococcus abyssi.
  J Biol Chem, 278, 31078-31087.  
14506262 K.A.Pattridge, C.H.Weber, J.A.Friesen, S.Sanker, C.Kent, and M.L.Ludwig (2003).
Glycerol-3-phosphate cytidylyltransferase. Structural changes induced by binding of CDP-glycerol and the role of lysine residues in catalysis.
  J Biol Chem, 278, 51863-51871.
PDB code: 1n1d
12595726 S.J.Eom, H.J.Ahn, H.W.Kim, S.H.Baek, and S.W.Suh (2003).
Crystallization and preliminary X-ray crystallographic studies of phosphopantetheine adenylyltransferase from Helicobacter pylori.
  Acta Crystallogr D Biol Crystallogr, 59, 561-562.  
12837781 T.Izard (2003).
A novel adenylate binding site confers phosphopantetheine adenylyltransferase interactions with coenzyme A.
  J Bacteriol, 185, 4074-4080.
PDB code: 1h1t
12574164 X.Zhang, O.V.Kurnasov, S.Karthikeyan, N.V.Grishin, A.L.Osterman, and H.Zhang (2003).
Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis.
  J Biol Chem, 278, 13503-13511.
PDB codes: 1nup 1nuq 1nur 1nus 1nut 1nuu
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.