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Transferase PDB id
1qr0
Jmol
Contents
Protein chain
228 a.a. *
Ligands
COA
Metals
_MG
Waters ×272
* Residue conservation analysis
PDB id:
1qr0
Name: Transferase
Title: Crystal structure of the 4'-phosphopantetheinyl transferase coenzyme a complex
Structure: 4'-phosphopantetheinyl transferase sfp. Chain: a. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Atcc: atcc21332. Gene: sfp. Expressed in: bacillus subtilis. Expression_system_taxid: 1423.
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.216     R-free:   0.278
Authors: K.Reuter,R.M.Mofid,A.M.Marahiel,R.Ficner
Key ref:
K.Reuter et al. (1999). Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4'-phosphopantetheinyl transferase superfamily. EMBO J, 18, 6823-6831. PubMed id: 10581256 DOI: 10.1093/emboj/18.23.6823
Date:
17-Jun-99     Release date:   10-Dec-99    
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  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     macromolecule biosynthetic process   3 terms 
  Biochemical function     transferase activity     4 terms  

 

 
DOI no: 10.1093/emboj/18.23.6823 EMBO J 18:6823-6831 (1999)
PubMed id: 10581256  
 
 
Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4'-phosphopantetheinyl transferase superfamily.
K.Reuter, M.R.Mofid, M.A.Marahiel, R.Ficner.
 
  ABSTRACT  
 
The Bacillus subtilis Sfp protein activates the peptidyl carrier protein (PCP) domains of surfactin synthetase by transferring the 4'-phosphopantetheinyl moiety of coenzyme A (CoA) to a serine residue conserved in all PCPs. Its wide PCP substrate spectrum renders Sfp a biotechnologically valuable enzyme for use in combinatorial non-ribosomal peptide synthesis. The structure of the Sfp-CoA complex determined at 1.8 A resolution reveals a novel alpha/beta-fold exhibiting an unexpected intramolecular 2-fold pseudosymmetry. This suggests a similar fold and dimerization mode for the homodimeric phosphopantetheinyl transferases such as acyl carrier protein synthase. The active site of Sfp accommodates a magnesium ion, which is complexed by the CoA pyrophosphate, the side chains of three acidic amino acids and one water molecule. CoA is bound in a fashion that differs in many aspects from all known CoA-protein complex structures. The structure reveals regions likely to be involved in the interaction with the PCP substrate.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 Stereo view of the experimental MAD electron density map covering CoA after solvent flattening contoured at 1.7 . The ribose is clearly present in a 3'-endo conformation leading to the axial orientation of the 2'-hydroxyl and the horizontal orientation of the 3'-phosphate group. Electron density can only be attributed for the two atoms of the pantetheinyl moiety nearest to the pyrophosphate. 		Figure 4.
Figure 4 Surface representation of SFP in a similar orientation to that in Figure 1A. Red represents a negative, and blue a positive electrostatic surface potential.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1999, 18, 6823-6831) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20966087 A.H.Asghar, S.Shastri, E.Dave, I.Wowk, K.Agnoli, A.M.Cook, and M.S.Thomas (2011).
The pobA gene of Burkholderia cenocepacia encodes a group I Sfp-type phosphopantetheinyltransferase required for biosynthesis of the siderophores ornibactin and pyochelin.
  Microbiology, 157, 349-361.  
20636978 S.Sugihara, Y.Orikasa, and H.Okuyama (2010).
The Escherichia coli highly expressed entD gene complements the pfaE deficiency in a pfa gene clone responsible for the biosynthesis of long-chain n-3 polyunsaturated fatty acids.
  FEMS Microbiol Lett, 307, 207-211.  
19562788 A.A.Roberts, J.N.Copp, M.A.Marahiel, and B.A.Neilan (2009).
The Synechocystis sp. PCC6803 Sfp-type phosphopantetheinyl transferase does not possess characteristic broad-range activity.
  Chembiochem, 10, 1869-1877.  
19636447 A.Koglin, and C.T.Walsh (2009).
Structural insights into nonribosomal peptide enzymatic assembly lines.
  Nat Prod Rep, 26, 987.  
19551180 J.L.Meier, and M.D.Burkart (2009).
The chemical biology of modular biosynthetic enzymes.
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19722489 M.Strieker, E.M.Nolan, C.T.Walsh, and M.A.Marahiel (2009).
Stereospecific synthesis of threo- and erythro-beta-hydroxyglutamic acid during kutzneride biosynthesis.
  J Am Chem Soc, 131, 13523-13530.  
19675886 M.Sunbul, and J.Yin (2009).
Site specific protein labeling by enzymatic posttranslational modification.
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19507202 M.Tosin, D.Spiteller, and J.B.Spencer (2009).
Malonyl carba(dethia)- and malonyl oxa(dethia)-coenzyme A as tools for trapping polyketide intermediates.
  Chembiochem, 10, 1714-1723.  
19573516 T.L.Foley, and M.D.Burkart (2009).
A homogeneous resonance energy transfer assay for phosphopantetheinyl transferase.
  Anal Biochem, 394, 39-47.  
19383706 V.Barbe, S.Cruveiller, F.Kunst, P.Lenoble, G.Meurice, A.Sekowska, D.Vallenet, T.Wang, I.Moszer, C.Médigue, and A.Danchin (2009).
From a consortium sequence to a unified sequence: the Bacillus subtilis 168 reference genome a decade later.
  Microbiology, 155, 1758-1775.  
18793461 C.A.Bottoms, and D.Xu (2008).
Wanted: unique names for unique atom positions. PDB-wide analysis of diastereotopic atom names of small molecules containing diphosphate.
  BMC Bioinformatics, 9, S16.  
18245839 N.R.De Lay, and J.E.Cronan (2008).
Genetic interaction between the Escherichia coli AcpT phosphopantetheinyl transferase and the YejM inner membrane protein.
  Genetics, 178, 1327-1337.  
18506874 P.Meiser, and R.Müller (2008).
Two functionally redundant Sfp-type 4'-phosphopantetheinyl transferases differentially activate biosynthetic pathways in Myxococcus xanthus.
  Chembiochem, 9, 1549-1553.  
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
18689472 Y.W.Lu, A.K.San Roman, and A.M.Gehring (2008).
Role of phosphopantetheinyl transferase genes in antibiotic production by Streptomyces coelicolor.
  J Bacteriol, 190, 6903-6908.  
17653358 A.C.Mercer, and M.D.Burkart (2007).
The ubiquitous carrier protein--a window to metabolite biosynthesis.
  Nat Prod Rep, 24, 750-773.  
18022563 G.Bunkoczi, S.Pasta, A.Joshi, X.Wu, K.L.Kavanagh, S.Smith, and U.Oppermann (2007).
Mechanism and substrate recognition of human holo ACP synthase.
  Chem Biol, 14, 1243-1253.
PDB codes: 2byd 2c43 2cg5
17448991 I.B.Lomakin, Y.Xiong, and T.A.Steitz (2007).
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  Cell, 129, 319-332.
PDB code: 2pff
17277172 O.Márquez-Fernández, A.Trigos, J.L.Ramos-Balderas, G.Viniegra-González, H.B.Deising, and J.Aguirre (2007).
Phosphopantetheinyl transferase CfwA/NpgA is required for Aspergillus nidulans secondary metabolism and asexual development.
  Eukaryot Cell, 6, 710-720.  
17171715 S.Wattanachaisaereekul, A.E.Lantz, M.L.Nielsen, O.S.Andrésson, and J.Nielsen (2007).
Optimization of heterologous production of the polyketide 6-MSA in Saccharomyces cerevisiae.
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16614225 A.Koglin, M.R.Mofid, F.Löhr, B.Schäfer, V.V.Rogov, M.M.Blum, T.Mittag, M.A.Marahiel, F.Bernhard, and V.Dötsch (2006).
Conformational switches modulate protein interactions in peptide antibiotic synthetases.
  Science, 312, 273-276.
PDB codes: 2gdw 2gdx 2gdy 2ge0 2ge1
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.  
16672613 H.A.Watkins, and E.N.Baker (2006).
Structural and functional analysis of Rv3214 from Mycobacterium tuberculosis, a protein with conflicting functional annotations, leads to its characterization as a phosphatase.
  J Bacteriol, 188, 3589-3599.
PDB code: 2a6p
16342318 I.Sielaff, A.Arnold, G.Godin, S.Tugulu, H.A.Klok, and K.Johnsson (2006).
Protein function microarrays based on self-immobilizing and self-labeling fusion proteins.
  Chembiochem, 7, 194-202.  
16597923 J.N.Copp, and B.A.Neilan (2006).
The phosphopantetheinyl transferase superfamily: phylogenetic analysis and functional implications in cyanobacteria.
  Appl Environ Microbiol, 72, 2298-2305.  
16774586 M.Welker, and H.von Döhren (2006).
Cyanobacterial peptides - nature's own combinatorial biosynthesis.
  FEMS Microbiol Rev, 30, 530-563.  
16824108 N.R.De Lay, and J.E.Cronan (2006).
A genome rearrangement has orphaned the Escherichia coli K-12 AcpT phosphopantetheinyl transferase from its cognate Escherichia coli O157:H7 substrates.
  Mol Microbiol, 61, 232-242.  
16460000 P.C.Dorrestein, J.Blackhall, P.D.Straight, M.A.Fischbach, S.Garneau-Tsodikova, D.J.Edwards, S.McLaughlin, M.Lin, W.H.Gerwick, R.Kolter, C.T.Walsh, and N.L.Kelleher (2006).
Activity screening of carrier domains within nonribosomal peptide synthetases using complex substrate mixtures and large molecule mass spectrometry.
  Biochemistry, 45, 1537-1546.  
17119639 P.C.Dorrestein, and N.L.Kelleher (2006).
Dissecting non-ribosomal and polyketide biosynthetic machineries using electrospray ionization Fourier-Transform mass spectrometry.
  Nat Prod Rep, 23, 893-918.  
16682444 U.Mechold, V.Ogryzko, S.Ngo, and A.Danchin (2006).
Oligoribonuclease is a common downstream target of lithium-induced pAp accumulation in Escherichia coli and human cells.
  Nucleic Acids Res, 34, 2364-2373.  
16128819 D.B.Stein, U.Linne, and M.A.Marahiel (2005).
Utility of epimerization domains for the redesign of nonribosomal peptide synthetases.
  FEBS J, 272, 4506-4520.  
15558647 N.Johnsson, N.George, and K.Johnsson (2005).
Protein chemistry on the surface of living cells.
  Chembiochem, 6, 47-52.  
15952903 S.W.White, J.Zheng, Y.M.Zhang, and Rock (2005).
The structural biology of type II fatty acid biosynthesis.
  Annu Rev Biochem, 74, 791-831.  
15975512 Y.Li, N.M.Llewellyn, R.Giri, F.Huang, and J.B.Spencer (2005).
Biosynthesis of the unique amino acid side chain of butirosin: possible protective-group chemistry in an acyl carrier protein-mediated pathway.
  Chem Biol, 12, 665-675.  
14695521 K.J.Weissman, H.Hong, M.Oliynyk, A.P.Siskos, and P.F.Leadlay (2004).
Identification of a phosphopantetheinyl transferase for erythromycin biosynthesis in Saccharopolyspora erythraea.
  Chembiochem, 5, 116-125.  
15487945 R.Finking, and M.A.Marahiel (2004).
Biosynthesis of nonribosomal peptides1.
  Annu Rev Microbiol, 58, 453-488.  
15066179 U.Linne, D.Schwarzer, G.N.Schroeder, and M.A.Marahiel (2004).
Mutational analysis of a type II thioesterase associated with nonribosomal peptide synthesis.
  Eur J Biochem, 271, 1536-1545.  
12815048 A.K.Joshi, L.Zhang, V.S.Rangan, and S.Smith (2003).
Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity.
  J Biol Chem, 278, 33142-33149.  
14645262 S.A.Sieber, and M.A.Marahiel (2003).
Learning from nature's drug factories: nonribosomal synthesis of macrocyclic peptides.
  J Bacteriol, 185, 7036-7043.  
12892891 S.Guo, and J.K.Bhattacharjee (2003).
Molecular characterization of the Candida albicans LYS5 gene and site-directed mutational analysis of the PPTase (Lys5p) domains for lysine biosynthesis.
  FEMS Microbiol Lett, 224, 261-267.  
14556641 S.L.Clugston, S.A.Sieber, M.A.Marahiel, and C.T.Walsh (2003).
Chirality of peptide bond-forming condensation domains in nonribosomal peptide synthetases: the C5 domain of tyrocidine synthetase is a (D)C(L) catalyst.
  Biochemistry, 42, 12095-12104.  
  12127488 H.D.Mootz, K.Schörgendorfer, and M.A.Marahiel (2002).
Functional characterization of 4'-phosphopantetheinyl transferase genes of bacterial and fungal origin by complementation of Saccharomyces cerevisiae lys5.
  FEMS Microbiol Lett, 213, 51-57.  
11867633 M.R.Mofid, R.Finking, and M.A.Marahiel (2002).
Recognition of hybrid peptidyl carrier proteins/acyl carrier proteins in nonribosomal peptide synthetase modules by the 4'-phosphopantetheinyl transferases AcpS and Sfp.
  J Biol Chem, 277, 17023-17031.  
12381736 R.Finking, J.Solsbacher, D.Konz, M.Schobert, A.Schafer, D.Jahn, and M.A.Marahiel (2002).
Characterization of a new type of phosphopantetheinyl transferase for fatty acid and siderophore synthesis in Pseudomonas aeruginosa.
  J Biol Chem, 277, 50293-50302.  
12023087 S.E.Lu, B.K.Scholz-Schroeder, and D.C.Gross (2002).
Construction of pMEKm12, an expression vector for protein production in Pseudomonas syringae.
  FEMS Microbiol Lett, 210, 115-121.  
11856321 V.Bergendahl, U.Linne, and M.A.Marahiel (2002).
Mutational analysis of the C-domain in nonribosomal peptide synthesis.
  Eur J Biochem, 269, 620-629.  
11451672 C.Sánchez, L.Du, D.J.Edwards, M.D.Toney, and B.Shen (2001).
Cloning and characterization of a phosphopantetheinyl transferase from Streptomyces verticillus ATCC15003, the producer of the hybrid peptide-polyketide antitumor drug bleomycin.
  Chem Biol, 8, 725-738.  
  11564558 H.Chen, S.O'Connor, D.E.Cane, and C.T.Walsh (2001).
Epothilone biosynthesis: assembly of the methylthiazolylcarboxy starter unit on the EpoB subunit.
  Chem Biol, 8, 899-912.  
11162233 S.Doekel, and M.A.Marahiel (2001).
Biosynthesis of natural products on modular peptide synthetases.
  Metab Eng, 3, 64-77.  
  10997907 K.D.Parris, L.Lin, A.Tam, R.Mathew, J.Hixon, M.Stahl, C.C.Fritz, J.Seehra, and W.S.Somers (2000).
Crystal structures of substrate binding to Bacillus subtilis holo-(acyl carrier protein) synthase reveal a novel trimeric arrangement of molecules resulting in three active sites.
  Structure, 8, 883-895.
PDB codes: 1f7l 1f7t 1f80
11032795 N.Y.Chirgadze, S.L.Briggs, K.A.McAllister, A.S.Fischl, and G.Zhao (2000).
Crystal structure of Streptococcus pneumoniae acyl carrier protein synthase: an essential enzyme in bacterial fatty acid biosynthesis.
  EMBO J, 19, 5281-5287.
PDB codes: 1fte 1ftf 1fth
10873839 S.Doekel, and M.A.Marahiel (2000).
Dipeptide formation on engineered hybrid peptide synthetases.
  Chem Biol, 7, 373-384.  
  10801488 T.Weber, R.Baumgartner, C.Renner, M.A.Marahiel, and T.A.Holak (2000).
Solution structure of PCP, a prototype for the peptidyl carrier domains of modular peptide synthetases.
  Structure, 8, 407-418.
PDB code: 1dny
10956034 U.Linne, and M.A.Marahiel (2000).
Control of directionality in nonribosomal peptide synthesis: role of the condensation domain in preventing misinitiation and timing of epimerization.
  Biochemistry, 39, 10439-10447.  
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.