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PDBsum entry 1b6t

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1b6t
Jmol
Contents
Protein chains
157 a.a. *
Ligands
SO4 ×3
COD
Waters ×322
* Residue conservation analysis
PDB id:
1b6t
Name: Transferase
Title: Phosphopantetheine adenylyltransferase in complex with 3'- dephospho-coa from escherichia coli
Structure: Protein (phosphopantetheine adenylyltransferase). Chain: a, b. Synonym: ppat, kdtb. Ec: 2.7.7.3
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Hexamer (from PDB file)
Resolution:
1.80Å     R-factor:   0.205     R-free:   0.235
Authors: T.Izard
Key ref:
T.Izard and A.Geerlof (1999). The crystal structure of a novel bacterial adenylyltransferase reveals half of sites reactivity. EMBO J, 18, 2021-2030. PubMed id: 10205156 DOI: 10.1093/emboj/18.8.2021
Date:
18-Jan-99     Release date:   19-Apr-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 Enzyme reactions 
   Enzyme class: E.C.2.7.7.3  - Pantetheine-phosphate adenylyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Coenzyme A Biosynthesis (late stages)
      Reaction: ATP + pantetheine 4'-phosphate = diphosphate + 3'-dephospho-CoA
ATP
Bound ligand (Het Group name = COD)
matches with 56.00% similarity
+ pantetheine 4'-phosphate
= 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  

 

 
    reference    
 
 
DOI no: 10.1093/emboj/18.8.2021 EMBO J 18:2021-2030 (1999)
PubMed id: 10205156  
 
 
The crystal structure of a novel bacterial adenylyltransferase reveals half of sites reactivity.
T.Izard, A.Geerlof.
 
  ABSTRACT  
 
Phosphopantetheine adenylyltransferase (PPAT) is an essential enzyme in bacteria that catalyses a rate-limiting step in coenzyme A (CoA) biosynthesis, by transferring an adenylyl group from ATP to 4'-phosphopantetheine, yielding dephospho-CoA (dPCoA). Each phosphopantetheine adenylyltransferase (PPAT) subunit displays a dinucleotide-binding fold that is structurally similar to that in class I aminoacyl-tRNA synthetases. Superposition of bound adenylyl moieties from dPCoA in PPAT and ATP in aminoacyl-tRNA synthetases suggests nucleophilic attack by the 4'-phosphopantetheine on the alpha-phosphate of ATP. The proposed catalytic mechanism implicates transition state stabilization by PPAT without involving functional groups of the enzyme in a chemical sense in the reaction. The crystal structure of the enzyme from Escherichia coli in complex with dPCoA shows that binding at one site causes a vice-like movement of active site residues lining the active site surface. The mode of enzyme product formation is highly concerted, with only one trimer of the PPAT hexamer showing evidence of dPCoA binding. The homologous active site attachment of ATP and the structural distribution of predicted sequence-binding motifs in PPAT classify the enzyme as belonging to the nucleotidyltransferase superfamily.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 The penultimate step in the CoA biosynthetic pathway. PPAT reversibly catalyses the adenylation by ATP of 4'-phosphopantetheine, forming 3'-dephospho-CoA and pyrophosphate.
Figure 3.
Figure 3 The PPAT hexamer. (A) Electrostatic surface potential (using the program GRASP; Nicholls et al., 1991) of the PPAT hexamer along the triad (red, negative; blue, positive; white, uncharged). The diameter along the 3-fold axis is 75 Å, with a channel across the entire hexamer with a diameter of at least 10 Å. The substrates and products must enter through this cavity to bind to the active site of the protein. Space-filling representations (using the program RASTER3D; Bacon and Anderson, 1988; Merritt and Murphy, 1994) looking down (B) the triad and (C) the dyad. Each of the six subunits is coloured differently.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1999, 18, 2021-2030) copyright 1999.  
  Figures were selected by an automated process.  

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.  
20382998 M.Schiltz, and G.Bricogne (2010).
;Broken symmetries' in macromolecular crystallography: phasing from unmerged data.
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19136717 S.Frago, A.Velázquez-Campoy, and M.Medina (2009).
The Puzzle of Ligand Binding to Corynebacterium ammoniagenes FAD Synthetase.
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18566507 M.Schiltz, and G.Bricogne (2008).
Exploiting the anisotropy of anomalous scattering boosts the phasing power of SAD and MAD experiments.
  Acta Crystallogr D Biol Crystallogr, 64, 711-729.  
18811972 S.Frago, M.Martínez-Júlvez, A.Serrano, and M.Medina (2008).
Structural analysis of FAD synthetase from Corynebacterium ammoniagenes.
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17873050 J.R.Miller, J.Ohren, R.W.Sarver, W.T.Mueller, P.de 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.  
16606823 C.Yuan, C.J.Rieke, G.Rimon, B.A.Wingerd, and W.L.Smith (2006).
Partnering between monomers of cyclooxygenase-2 homodimers.
  Proc Natl Acad Sci U S A, 103, 6142-6147.  
  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.
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16648134 Y.M.Zhang, S.W.White, and C.O.Rock (2006).
Inhibiting bacterial fatty acid synthesis.
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15678099 S.C.Sinha, M.Wetterer, S.R.Sprang, J.E.Schultz, and J.U.Linder (2005).
Origin of asymmetry in adenylyl cyclases: structures of Mycobacterium tuberculosis Rv1900c.
  EMBO J, 24, 663-673.
PDB codes: 1ybt 1ybu
15468322 W.Wang, R.Kim, H.Yokota, and S.H.Kim (2005).
Crystal structure of flavin binding to FAD synthetase of Thermotoga maritima.
  Proteins, 58, 246-248.
PDB code: 1s4m
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
15136582 R.A.Ivey, Y.M.Zhang, K.G.Virga, K.Hevener, R.E.Lee, C.O.Rock, S.Jackowski, and H.W.Park (2004).
The structure of the pantothenate kinase.ADP.pantothenate ternary complex reveals the relationship between the binding sites for substrate, allosteric regulator, and antimetabolites.
  J Biol Chem, 279, 35622-35629.
PDB code: 1sq5
15083156 S.A.Ralph, G.G.van Dooren, R.F.Waller, M.J.Crawford, M.J.Fraunholz, B.J.Foth, C.J.Tonkin, D.S.Roos, and G.I.McFadden (2004).
Tropical infectious diseases: metabolic maps and functions of the Plasmodium falciparum apicoplast.
  Nat Rev Microbiol, 2, 203-216.  
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
15459190 Y.M.Zhang, M.W.Frank, K.G.Virga, R.E.Lee, C.O.Rock, and S.Jackowski (2004).
Acyl carrier protein is a cellular target for the antibacterial action of the pantothenamide class of pantothenate antimetabolites.
  J Biol Chem, 279, 50969-50975.  
12517446 A.Krupa, K.Sandhya, N.Srinivasan, and S.Jonnalagadda (2003).
A conserved domain in prokaryotic bifunctional FAD synthetases can potentially catalyze nucleotide transfer.
  Trends Biochem Sci, 28, 9.  
12754240 C.O.Rock, H.W.Park, and S.Jackowski (2003).
Role of feedback regulation of pantothenate kinase (CoaA) in control of coenzyme A levels in Escherichia coli.
  J Bacteriol, 185, 3410-3415.  
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
12906824 N.Manoj, E.Strauss, T.P.Begley, and S.E.Ealick (2003).
Structure of human phosphopantothenoylcysteine synthetase at 2.3 A resolution.
  Structure, 11, 927-936.
PDB code: 1p9o
12538896 N.O'Toole, J.A.Barbosa, Y.Li, L.W.Hung, A.Matte, and M.Cygler (2003).
Crystal structure of a trimeric form of dephosphocoenzyme A kinase from Escherichia coli.
  Protein Sci, 12, 327-336.
PDB code: 1n3b
12906818 N.O'Toole, and M.Cygler (2003).
The final player in the coenzyme A biosynthetic pathway.
  Structure, 11, 899-900.  
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
12810729 V.Saridakis, and E.F.Pai (2003).
Mutational, structural, and kinetic studies of the ATP-binding site of Methanobacterium thermoautotrophicum nicotinamide mononucleotide adenylyltransferase.
  J Biol Chem, 278, 34356-34363.
PDB codes: 1m8f 1m8g 1m8j 1m8k
11980892 A.Zhyvoloup, I.Nemazanyy, A.Babich, G.Panasyuk, N.Pobigailo, M.Vudmaska, V.Naidenov, O.Kukharenko, S.Palchevskii, L.Savinska, G.Ovcharenko, F.Verdier, T.Valovka, T.Fenton, H.Rebholz, M.L.Wang, P.Shepherd, G.Matsuka, V.Filonenko, and I.T.Gout (2002).
Molecular cloning of CoA Synthase. The missing link in CoA biosynthesis.
  J Biol Chem, 277, 22107-22110.  
12012333 L.Aravind, V.Anantharaman, and E.V.Koonin (2002).
Monophyly of class I aminoacyl tRNA synthetase, USPA, ETFP, photolyase, and PP-ATPase nucleotide-binding domains: implications for protein evolution in the RNA.
  Proteins, 48, 1.  
11923312 M.Daugherty, B.Polanuyer, M.Farrell, M.Scholle, A.Lykidis, V.de Crécy-Lagard, and A.Osterman (2002).
Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics.
  J Biol Chem, 277, 21431-21439.  
11751893 S.Garavaglia, I.D'Angelo, M.Emanuelli, F.Carnevali, F.Pierella, G.Magni, and M.Rizzi (2002).
Structure of human NMN adenylyltransferase. A key nuclear enzyme for NAD homeostasis.
  J Biol Chem, 277, 8524-8530.
PDB code: 1kku
12068016 S.K.Singh, O.V.Kurnasov, B.Chen, H.Robinson, N.V.Grishin, A.L.Osterman, and H.Zhang (2002).
Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities.
  J Biol Chem, 277, 33291-33299.
PDB code: 1lw7
12142426 S.Y.Gerdes, M.D.Scholle, M.D'Souza, A.Bernal, M.V.Baev, M.Farrell, O.V.Kurnasov, M.D.Daugherty, F.Mseeh, B.M.Polanuyer, J.W.Campbell, S.Anantha, K.Y.Shatalin, S.A.Chowdhury, M.Y.Fonstein, and A.L.Osterman (2002).
From genetic footprinting to antimicrobial drug targets: examples in cofactor biosynthetic pathways.
  J Bacteriol, 184, 4555-4572.  
11931774 W.T.Watson, T.D.Minogue, D.L.Val, S.B.von Bodman, and M.E.Churchill (2002).
Structural basis and specificity of acyl-homoserine lactone signal production in bacterial quorum sensing.
  Mol Cell, 9, 685-694.
PDB codes: 1k4j 1kzf
11377204 F.von Delft, A.Lewendon, V.Dhanaraj, T.L.Blundell, C.Abell, and A.G.Smith (2001).
The crystal structure of E. coli pantothenate synthetase confirms it as a member of the cytidylyltransferase superfamily.
  Structure, 9, 439-450.
PDB code: 1iho
11389593 I.J.MacRae, I.H.Segel, and A.J.Fisher (2001).
Crystal structure of ATP sulfurylase from Penicillium chrysogenum: insights into the allosteric regulation of sulfate assimilation.
  Biochemistry, 40, 6795-6804.
PDB code: 1i2d
11292795 P.Mishra, P.K.Park, and D.G.Drueckhammer (2001).
Identification of yacE (coaE) as the structural gene for dephosphocoenzyme A kinase in Escherichia coli K-12.
  J Bacteriol, 183, 2774-2778.  
11157739 T.C.Ullrich, M.Blaesse, and R.Huber (2001).
Crystal structure of ATP sulfurylase from Saccharomyces cerevisiae, a key enzyme in sulfate activation.
  EMBO J, 20, 316-329.
PDB codes: 1g8f 1g8g 1g8h
10986466 I.D'Angelo, N.Raffaelli, V.Dabusti, T.Lorenzi, G.Magni, and M.Rizzi (2000).
Structure of nicotinamide mononucleotide adenylyltransferase: a key enzyme in NAD(+) biosynthesis.
  Structure, 8, 993.
PDB code: 1f9a
11058040 K.W.Vogel, L.M.Stark, P.K.Mishra, W.Yang, and D.G.Drueckhammer (2000).
Investigating the role of the geminal dimethyl groups of coenzyme A: synthesis and studies of a didemethyl analogue.
  Bioorg Med Chem, 8, 2451-2460.  
10629197 M.A.Valvano, C.L.Marolda, M.Bittner, M.Glaskin-Clay, T.L.Simon, and J.D.Klena (2000).
The rfaE gene from Escherichia coli encodes a bifunctional protein involved in biosynthesis of the lipopolysaccharide core precursor ADP-L-glycero-D-manno-heptose.
  J Bacteriol, 182, 488-497.  
10480925 A.Geerlof, A.Lewendon, and W.V.Shaw (1999).
Purification and characterization of phosphopantetheine adenylyltransferase from Escherichia coli.
  J Biol Chem, 274, 27105-27111.  
10508782 C.H.Weber, Y.S.Park, S.Sanker, C.Kent, and M.L.Ludwig (1999).
A prototypical cytidylyltransferase: CTP:glycerol-3-phosphate cytidylyltransferase from bacillus subtilis.
  Structure, 7, 1113-1124.
PDB code: 1coz
10531525 N.Chandra, K.R.Acharya, and P.C.Moody (1999).
Analysis and characterization of data from twinned crystals.
  Acta Crystallogr D Biol Crystallogr, 55, 1750-1758.  
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 codes are shown on the right.