PDBsum entry 1w57

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protein ligands metals links
Transferase PDB id
Protein chain
368 a.a. *
C5P ×2
Waters ×57
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structure of the bifunctional ispdf from campylobacter jejuni containing zn
Structure: Ispd/ispf bifunctional enzyme. Chain: a. Synonym: 2-c-methyl-d-erythritol 4-phosphate cytidylyltransferase, 4-diphosphocytidyl-2c-methyl-d- erythritol synthase, mep cytidylyltransferase, mct, 2-c-methyl-d-erythritol 2,4-cyclodiphosphate synthase, mecps, mecdp-synthase, methylerythritol 4-phosphate cytidylyltransferase, methylerythritol 2,4- cyclodiphosphate synthase.
Source: Campylobacter jejuni. Organism_taxid: 197. Strain: jejuni ntct 11168. Atcc: 33560. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Hexamer (from PDB file)
3.09Å     R-factor:   0.221     R-free:   0.295
Authors: M.Gabrielsen,C.S.Bond,W.N.Hunter
Key ref:
M.Gabrielsen et al. (2004). Hexameric assembly of the bifunctional methylerythritol 2,4-cyclodiphosphate synthase and protein-protein associations in the deoxy-xylulose-dependent pathway of isoprenoid precursor biosynthesis. J Biol Chem, 279, 52753-52761. PubMed id: 15466439 DOI: 10.1074/jbc.M408895200
06-Aug-04     Release date:   04-Oct-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9PM68  (ISPDF_CAMJE) -  Bifunctional enzyme IspD/IspF
371 a.a.
368 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.  - 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: CTP + 2-C-methyl-D-erythritol 4-phosphate = diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
Bound ligand (Het Group name = C5P)
matches with 72.00% similarity
+ 2-C-methyl-D-erythritol 4-phosphate
Bound ligand (Het Group name = GPP)
matches with 47.00% similarity
+ 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
      Cofactor: Mn(2+) or Mg(2+)
   Enzyme class 2: E.C.  - 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol = 2-C-methyl- D-erythritol 2,4-cyclodiphosphate + CMP
2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
2-C-methyl- D-erythritol 2,4-cyclodiphosphate
Bound ligand (Het Group name = GPP)
matches with 66.00% similarity
Bound ligand (Het Group name = C5P)
corresponds exactly
      Cofactor: Mn(2+) or Mg(2+)
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     7 terms  


DOI no: 10.1074/jbc.M408895200 J Biol Chem 279:52753-52761 (2004)
PubMed id: 15466439  
Hexameric assembly of the bifunctional methylerythritol 2,4-cyclodiphosphate synthase and protein-protein associations in the deoxy-xylulose-dependent pathway of isoprenoid precursor biosynthesis.
M.Gabrielsen, C.S.Bond, I.Hallyburton, S.Hecht, A.Bacher, W.Eisenreich, F.Rohdich, W.N.Hunter.
The bifunctional methylerythritol 4-phosphate cytidylyltransferase methylerythritol 2,4-cyclodiphosphate synthase (IspDF) is unusual in that it catalyzes nonconsecutive reactions in the 1-deoxy-D-xylulose 5-phosphate (DOXP) pathway of isoprenoid precursor biosynthesis. The crystal structure of IspDF from the bacterial pathogen Campylobacter jejuni reveals an elongated hexamer with D3 symmetry compatible with the dimeric 2C-methyl-D-erythritol-4-phosphate cytidylyltransferase and trimeric 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase monofunctional enzymes. Complex formation of IspDF with 4-diphosphocytidyl-2C-methyl-D-erythritol kinase (IspE), the intervening enzyme activity in the pathway, has been observed in solution for the enzymes from C. jejuni and Agrobacterium tumefaciens. The monofunctional enzymes (2C-methyl-D-erythritol-4-phosphate cytidylyltransferase, IspE, and 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase) involved in the DOXP biosynthetic pathway of Escherichia coli also show physical associations. We propose that complex formation of the three enzymes at the core of the DOXP pathway can produce an assembly localizing 18 catalytic centers for the early stages of isoprenoid biosynthesis.
  Selected figure(s)  
Figure 1.
FIG. 1. The three reactions catalyzed by the IspDEF enzyme activities in isoprenoid precursor biosynthesis by the DOXP pathway.
Figure 3.
FIG. 3. Structure of the IspDF hexamer. a, stereoview depiction viewed parallel to one of the 2-fold axis. Subunits are colored separately and labeled A to F. Helices are shown as cylinders, -strands are shown as arrows, metal ions are shown as spheres, and GPP and CMP are shown as green and yellow sticks. b, view parallel to the molecular 3-fold axis.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 52753-52761) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20213667 V.Giménez-Oya, O.Villacañas, C.Obiol-Pardo, M.Antolin-Llovera, J.Rubio-Martinez, and S.Imperial (2011).
Design of novel ligands of CDP-methylerythritol kinase by mimicking direct protein-protein and solvent-mediated interactions.
  J Mol Recognit, 24, 71-80.  
19916033 C.Obiol-Pardo, A.Cordero, J.Rubio-Martinez, and S.Imperial (2010).
Homology modeling of Mycobacterium tuberculosis 2C-methyl-D-erythritol-4-phosphate cytidylyltransferase, the third enzyme in the MEP pathway for isoprenoid biosynthesis.
  J Mol Model, 16, 1061-1073.  
  20208151 J.Kalinowska-Tłuścik, L.Miallau, M.Gabrielsen, G.A.Leonard, S.M.McSweeney, and W.N.Hunter (2010).
A triclinic crystal form of Escherichia coli 4-diphosphocytidyl-2C-methyl-D-erythritol kinase and reassessment of the quaternary structure.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 66, 237-241.
PDB code: 2ww4
18793870 H.Eoh, P.J.Brennan, and D.C.Crick (2009).
The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target.
  Tuberculosis (Edinb), 89, 1.  
19320487 N.L.Ramsden, L.Buetow, A.Dawson, L.A.Kemp, V.Ulaganathan, R.Brenk, G.Klebe, and W.N.Hunter (2009).
A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy.
  J Med Chem, 52, 2531-2542.
PDB codes: 3elc 3eor 3ern 3esj 3fba
19198899 V.Giménez-Oya, O.Villacañas, X.Fernàndez-Busquets, J.Rubio-Martinez, and S.Imperial (2009).
Mimicking direct protein-protein and solvent-mediated interactions in the CDP-methylerythritol kinase homodimer: a pharmacophore-directed virtual screening approach.
  J Mol Model, 15, 997.  
17660251 B.M.Calisto, J.Perez-Gil, M.Bergua, J.Querol-Audi, I.Fita, and S.Imperial (2007).
Biosynthesis of isoprenoids in plants: structure of the 2C-methyl-D-erithrytol 2,4-cyclodiphosphate synthase from Arabidopsis thaliana. Comparison with the bacterial enzymes.
  Protein Sci, 16, 2082-2088.
PDB code: 2pmp
17956607 L.Buetow, A.C.Brown, T.Parish, and W.N.Hunter (2007).
The structure of Mycobacteria 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, an essential enzyme, provides a platform for drug discovery.
  BMC Struct Biol, 7, 68.
PDB code: 2uzh
17360612 T.Toyomasu, M.Tsukahara, A.Kaneko, R.Niida, W.Mitsuhashi, T.Dairi, N.Kato, and T.Sassa (2007).
Fusicoccins are biosynthesized by an unusual chimera diterpene synthase in fungi.
  Proc Natl Acad Sci U S A, 104, 3084-3088.  
16533036 C.Lherbet, F.Pojer, S.B.Richard, J.P.Noel, and C.D.Poulter (2006).
Absence of substrate channeling between active sites in the Agrobacterium tumefaciens IspDF and IspE enzymes of the methyl erythritol phosphate pathway.
  Biochemistry, 45, 3548-3553.  
16478479 M.Gabrielsen, J.Kaiser, F.Rohdich, W.Eisenreich, R.Laupitz, A.Bacher, C.S.Bond, and W.N.Hunter (2006).
The crystal structure of a plant 2C-methyl-D-erythritol 4-phosphate cytidylyltransferase exhibits a distinct quaternary structure compared to bacterial homologues and a possible role in feedback regulation for cytidine monophosphate.
  FEBS J, 273, 1065-1073.
PDB code: 1w77
16231155 M.H.Hsieh, and H.M.Goodman (2006).
Functional evidence for the involvement of Arabidopsis IspF homolog in the nonmevalonate pathway of plastid isoprenoid biosynthesis.
  Planta, 223, 779-784.  
  16511114 T.Sgraja, L.E.Kemp, N.Ramsden, and W.N.Hunter (2005).
A double mutation of Escherichia coli2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase disrupts six hydrogen bonds with, yet fails to prevent binding of, an isoprenoid diphosphate.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 625-629.
PDB code: 1yqn
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.