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PDBsum entry 2ge0
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protein ligands metals links
Transferase PDB id
2ge0

 

 

 

 

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Contents
Protein chain
228 a.a.
Ligands
COA
Metals
_MG
Theoretical model
PDB id:
2ge0
Name: Transferase
Title: Active complex of coenzyme a and the pptase sfp from b. Subtilis
Structure: 4'-phosphopantetheinyl transferase sfp. Chain: a. Synonym: surfactin synthetase-activating enzyme. Ec: 2.7.8.-
Source: Bacillus subtilis. Bacteria. Genus: sfp, lpa-8. Strain: atcc 21332
Authors: A.Koglin,M.-M.Blum,V.V.Rogov,M.A.Marahiel,F.Bernhard, V.Doetsch
Key ref:
A.Koglin et al. (2006). Conformational switches modulate protein interactions in peptide antibiotic synthetases. Science, 312, 273-276. PubMed id: 16614225 DOI: 10.1126/science.1122928
Date:
17-Mar-06     Release date:   01-Aug-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P39135  (SFP_BACSU) -  4'-phosphopantetheinyl transferase sfp
Seq:
Struc: 		224 a.a.
228 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 

 
DOI no: 10.1126/science.1122928 Science 312:273-276 (2006)
PubMed id: 16614225  
 
 
Conformational switches modulate protein interactions in peptide antibiotic synthetases.
A.Koglin, M.R.Mofid, F.Löhr, B.Schäfer, V.V.Rogov, M.M.Blum, T.Mittag, M.A.Marahiel, F.Bernhard, V.Dötsch.
 
  ABSTRACT  
 
Protein dynamics plays an important role in protein function. Many functionally important motions occur on the microsecond and low millisecond time scale and can be characterized by nuclear magnetic resonance relaxation experiments. We describe the different states of a peptidyl carrier protein (PCP) that play a crucial role in its function as a peptide shuttle in the nonribosomal peptide synthetases of the tyrocidine A system. Both apo-PCP (without the bound 4'-phosphopantetheine cofactor) and holo-PCP exist in two different stable conformations. We show that one of the apo conformations and one of the holo conformations are identical, whereas the two remaining conformations are only detectable by nuclear magnetic resonance spectroscopy in either the apo or holo form. We further demonstrate that this conformational diversity is an essential prerequisite for the directed movement of the 4'-PP cofactor and its interaction with externally acting proteins such as thioesterases and 4'-PP transferase.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Ribbon diagrams of the average NMR solution structures of the TycC3-PCP conformers in the A, A/H, and H states. 		Figure 4.
Fig. 4. Model of the A-state TycC3-PCP/Sfp complex. The Sfp protein is shown in yellow, TycC3-PCP in blue, and CoA in red. The arrow indicates the position of the reactive thiol group of CoA. (A) Proposed position of CoA in Sfp based on the electron density of the adenyl phosphorus in the Sfp crystal structure (11) and calculations with the program auto-Dock 3 (27). (B) Space-filling model of the Sfp/A-state TycC3-PCP complex.
 
  The above figures are reprinted by permission from the AAAs: Science (2006, 312, 273-276) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21184004 A.S.Worthington, G.H.Hur, and M.D.Burkart (2011).
Activity-guided engineering of natural product carrier proteins.
  Mol Biosyst, 7, 365-370.  
21513883 T.Velkov, J.Horne, M.J.Scanlon, B.Capuano, E.Yuriev, and A.Lawen (2011).
Characterization of the N-methyltransferase activities of the multifunctional polypeptide cyclosporin synthetase.
  Chem Biol, 18, 464-475.  
20662770 D.I.Chan, and H.J.Vogel (2010).
Current understanding of fatty acid biosynthesis and the acyl carrier protein.
  Biochem J, 430, 1.  
20659690 E.Płoskoń, C.J.Arthur, A.L.Kanari, P.Wattana-amorn, C.Williams, J.Crosby, T.J.Simpson, C.L.Willis, and M.P.Crump (2010).
Recognition of intermediate functionality by acyl carrier protein over a complete cycle of fatty acid biosynthesis.
  Chem Biol, 17, 776-785.
PDB codes: 2koo 2kop 2koq 2kor 2kos
20659683 L.Tran, R.W.Broadhurst, M.Tosin, A.Cavalli, and K.J.Weissman (2010).
Insights into protein-protein and enzyme-substrate interactions in modular polyketide synthases.
  Chem Biol, 17, 705-716.  
20731893 T.Maier, M.Leibundgut, D.Boehringer, and N.Ban (2010).
Structure and function of eukaryotic fatty acid synthases.
  Q Rev Biophys, 43, 373-422.  
19636447 A.Koglin, and C.T.Walsh (2009).
Structural insights into nonribosomal peptide enzymatic assembly lines.
  Nat Prod Rep, 26, 987.  
  19610673 A.M.Gulick (2009).
Conformational dynamics in the Acyl-CoA synthetases, adenylation domains of non-ribosomal peptide synthetases, and firefly luciferase.
  ACS Chem Biol, 4, 811-827.  
  19177367 B.N.Wu, Y.M.Zhang, C.O.Rock, and J.J.Zheng (2009).
Structural modification of acyl carrier protein by butyryl group.
  Protein Sci, 18, 240-246.
PDB codes: 2k92 2k93 2k94
19217343 C.Khosla, S.Kapur, and D.E.Cane (2009).
Revisiting the modularity of modular polyketide synthases.
  Curr Opin Chem Biol, 13, 135-143.  
19841628 D.D.Boehr, R.Nussinov, and P.E.Wright (2009).
The role of dynamic conformational ensembles in biomolecular recognition.
  Nat Chem Biol, 5, 789-796.  
19728110 D.P.Frueh, A.Leed, H.Arthanari, A.Koglin, C.T.Walsh, and G.Wagner (2009).
Time-shared HSQC-NOESY for accurate distance constraints measured at high-field in (15)N-(13)C-ILV methyl labeled proteins.
  J Biomol NMR, 45, 311-318.  
19801192 G.Fuentes, and A.Valencia (2009).
Ras classical effectors: new tales from in silico complexes.
  Trends Biochem Sci, 34, 533-539.  
19551180 J.L.Meier, and M.D.Burkart (2009).
The chemical biology of modular biosynthetic enzymes.
  Chem Soc Rev, 38, 2012-2045.  
19156787 M.Strieker, and M.A.Marahiel (2009).
The structural diversity of acidic lipopeptide antibiotics.
  Chembiochem, 10, 607-616.  
19169353 S.K.Parker, R.M.Barkley, J.G.Rino, and M.L.Vasil (2009).
Mycobacterium tuberculosis Rv3802c encodes a phospholipase/thioesterase and is inhibited by the antimycobacterial agent tetrahydrolipstatin.
  PLoS ONE, 4, e4281.  
18704089 A.Koglin, F.Löhr, F.Bernhard, V.V.Rogov, D.P.Frueh, E.R.Strieter, M.R.Mofid, P.Güntert, G.Wagner, C.T.Walsh, M.A.Marahiel, and V.Dötsch (2008).
Structural basis for the selectivity of the external thioesterase of the surfactin synthetase.
  Nature, 454, 907-911.
PDB code: 2k2q
18583577 A.Tanovic, S.A.Samel, L.O.Essen, and M.A.Marahiel (2008).
Crystal structure of the termination module of a nonribosomal peptide synthetase.
  Science, 321, 659-663.
PDB code: 2vsq
18704088 D.P.Frueh, H.Arthanari, A.Koglin, D.A.Vosburg, A.E.Bennett, C.T.Walsh, and G.Wagner (2008).
Dynamic thiolation-thioesterase structure of a non-ribosomal peptide synthetase.
  Nature, 454, 903-906.
PDB code: 2roq
17868092 G.R.Marshall, J.A.Feng, and D.J.Kuster (2008).
Back to the future: ribonuclease A.
  Biopolymers, 90, 259-277.  
18357594 K.J.Weissman, and R.Müller (2008).
Protein-protein interactions in multienzyme megasynthetases.
  Chembiochem, 9, 826-848.  
18948193 M.Leibundgut, T.Maier, S.Jenni, and N.Ban (2008).
The multienzyme architecture of eukaryotic fatty acid synthases.
  Curr Opin Struct Biol, 18, 714-725.  
18770515 S.E.Evans, C.Williams, C.J.Arthur, S.G.Burston, T.J.Simpson, J.Crosby, and M.P.Crump (2008).
An ACP structural switch: conformational differences between the apo and holo forms of the actinorhodin polyketide synthase acyl carrier protein.
  Chembiochem, 9, 2424-2432.
PDB codes: 2k0x 2k0y
18704072 S.Kapur, and C.Khosla (2008).
Biochemistry: Fit for an enzyme.
  Nature, 454, 832-833.  
17653358 A.C.Mercer, and M.D.Burkart (2007).
The ubiquitous carrier protein--a window to metabolite biosynthesis.
  Nat Prod Rep, 24, 750-773.  
17576425 B.Wilkinson, and J.Micklefield (2007).
Mining and engineering natural-product biosynthetic pathways.
  Nat Chem Biol, 3, 379-386.  
17606920 Z.Zhou, J.R.Lai, and C.T.Walsh (2007).
Directed evolution of aryl carrier proteins in the enterobactin synthetase.
  Proc Natl Acad Sci U S A, 104, 11621-11626.  
16952189 D.B.Stein, U.Linne, M.Hahn, and M.A.Marahiel (2006).
Impact of epimerization domains on the intermodular transfer of enzyme-bound intermediates in nonribosomal peptide synthesis.
  Chembiochem, 7, 1807-1814.  
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.

 

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