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PDBsum entry 1f80

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protein metals Protein-protein interface(s) links
Transferase PDB id
1f80
Jmol
Contents
Protein chains
118 a.a. *
74 a.a. *
Metals
_NA
Waters ×124
* Residue conservation analysis
PDB id:
1f80
Name: Transferase
Title: Holo-(acyl carrier protein) synthase in complex with holo- (acyl carrier protein)
Structure: Holo-(acyl carrier protein) synthase. Chain: a, b, c. Engineered: yes. Mutation: yes. Acyl carrier protein. Chain: d, e, f. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Hexamer (from PQS)
Resolution:
2.30Å     R-factor:   0.222     R-free:   0.279
Authors: K.D.Parris,L.Lin,A.Tam,R.Mathew,J.Hixon,M.Stahl,C.C.Fritz, J.Seehra,W.S.Somers
Key ref:
K.D.Parris et al. (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. PubMed id: 10997907 DOI: 10.1016/S0969-2126(00)00178-7
Date:
28-Jun-00     Release date:   28-Jun-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P96618  (ACPS_BACSU) -  Holo-[acyl-carrier-protein] synthase
Seq:
Struc:
121 a.a.
118 a.a.*
Protein chains
Pfam   ArchSchema ?
P80643  (ACP_BACSU) -  Acyl carrier protein
Seq:
Struc:
77 a.a.
74 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C: E.C.2.7.8.7  - Holo-[acyl-carrier-protein] synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: CoA-(4'-phosphopantetheine) + apo-[acyl-carrier-protein] = adenosine 3',5'-bisphosphate + holo-[acyl-carrier-protein]
CoA-(4'-phosphopantetheine)
+ apo-[acyl-carrier-protein]
= adenosine 3',5'-bisphosphate
+ holo-[acyl-carrier-protein]
      Cofactor: Mg(2+)
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     lipid metabolic process   4 terms 
  Biochemical function     transferase activity     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/S0969-2126(00)00178-7 Structure 8:883-895 (2000)
PubMed id: 10997907  
 
 
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.
K.D.Parris, L.Lin, A.Tam, R.Mathew, J.Hixon, M.Stahl, C.C.Fritz, J.Seehra, W.S.Somers.
 
  ABSTRACT  
 
BACKGROUND: Holo-(acyl carrier protein) synthase (AcpS), a member of the phosphopantetheinyl transferase superfamily, plays a crucial role in the functional activation of acyl carrier protein (ACP) in the fatty acid biosynthesis pathway. AcpS catalyzes the attachment of the 4'-phosphopantetheinyl moiety of coenzyme A (CoA) to the sidechain of a conserved serine residue on apo-ACP. RESULTS: We describe here the first crystal structure of a type II ACP from Bacillus subtilis in complex with its activator AcpS at 2.3 A. We also have determined the structures of AcpS alone (at 1.8 A) and AcpS in complex with CoA (at 1.5 A). These structures reveal that AcpS exists as a trimer. A catalytic center is located at each of the solvent-exposed interfaces between AcpS molecules. Site-directed mutagenesis studies confirm the importance of trimer formation in AcpS activity. CONCLUSIONS: The active site in AcpS is only formed when two AcpS molecules dimerize. The addition of a third molecule allows for the formation of two additional active sites and also permits a large hydrophobic surface from each molecule of AcpS to be buried in the trimer. The mutations Ile5-->Arg, Gln113-->Glu and Gln113-->Arg show that AcpS is inactive when unable to form a trimer. The co-crystal structures of AcpS-CoA and AcpS-ACP allow us to propose a catalytic mechanism for this class of 4'-phosphopantetheinyl transferases.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. The mechanism that can be derived from the crystal structures in this study. The metal-bound water molecule removes the hydrogen from Ser36, converting it into a nucleophile and thereby initiating P-pant transfer and activation of ACP.
 
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 883-895) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22993090 A.S.Halavaty, Y.Kim, G.Minasov, L.Shuvalova, I.Dubrovska, J.Winsor, M.Zhou, O.Onopriyenko, T.Skarina, L.Papazisi, K.Kwon, S.N.Peterson, A.Joachimiak, A.Savchenko, and W.F.Anderson (2012).
Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria.
  Acta Crystallogr D Biol Crystallogr, 68, 1359-1370.
PDB codes: 3f09 3hyk 3qmn 4jm7
20662770 D.I.Chan, and H.J.Vogel (2010).
Current understanding of fatty acid biosynthesis and the acyl carrier protein.
  Biochem J, 430, 1.  
20013982 J.A.Shields, A.S.Rahman, C.J.Arthur, J.Crosby, J.Hothersall, T.J.Simpson, and C.M.Thomas (2010).
Phosphopantetheinylation and specificity of acyl carrier proteins in the mupirocin biosynthetic cluster.
  Chembiochem, 11, 248-255.  
  19768685 J.R.Gallagher, and S.T.Prigge (2010).
Plasmodium falciparum acyl carrier protein crystal structures in disulfide-linked and reduced states and their prevalence during blood stage growth.
  Proteins, 78, 575-588.
PDB codes: 3gzl 3gzm
19933275 K.C.Strickland, L.A.Hoeferlin, N.V.Oleinik, N.I.Krupenko, and S.A.Krupenko (2010).
Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase.
  J Biol Chem, 285, 1627-1633.  
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.  
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.  
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
18561189 J.G.McCoy, H.D.Johnson, S.Singh, C.A.Bingman, I.K.Lei, J.S.Thorson, and G.N.Phillips (2009).
Structural characterization of CalO2: a putative orsellinic acid P450 oxidase in the calicheamicin biosynthetic pathway.
  Proteins, 74, 50-60.
PDB code: 3buj
19675886 M.Sunbul, and J.Yin (2009).
Site specific protein labeling by enzymatic posttranslational modification.
  Org Biomol Chem, 7, 3361-3371.  
19381365 P.Beltran-Alvarez, C.J.Arthur, R.J.Cox, J.Crosby, M.P.Crump, and T.J.Simpson (2009).
Preliminary kinetic analysis of acyl carrier protein-ketoacylsynthase interactions in the actinorhodin minimal polyketide synthase.
  Mol Biosyst, 5, 511-518.  
19520851 S.K.Upadhyay, A.Misra, R.Srivastava, N.Surolia, A.Surolia, and M.Sundd (2009).
Structural insights into the acyl intermediates of the Plasmodium falciparum fatty acid synthesis pathway: the mechanism of expansion of the acyl carrier protein core.
  J Biol Chem, 284, 22390-22400.  
19573516 T.L.Foley, and M.D.Burkart (2009).
A homogeneous resonance energy transfer assay for phosphopantetheinyl transferase.
  Anal Biochem, 394, 39-47.  
18809688 D.I.Chan, T.Stockner, D.P.Tieleman, and H.J.Vogel (2008).
Molecular Dynamics Simulations of the Apo-, Holo-, and Acyl-forms of Escherichia coli Acyl Carrier Protein.
  J Biol Chem, 283, 33620-33629.  
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.  
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
18059524 D.M.Byers, and H.Gong (2007).
Acyl carrier protein: structure-function relationships in a conserved multifunctional protein family.
  Biochem Cell Biol, 85, 649-662.  
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
17179150 H.Gong, A.Murphy, C.R.McMaster, and D.M.Byers (2007).
Neutralization of acidic residues in helix II stabilizes the folded conformation of acyl carrier protein and variably alters its function with different enzymes.
  J Biol Chem, 282, 4494-4503.  
17448991 I.B.Lomakin, Y.Xiong, and T.A.Steitz (2007).
The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together.
  Cell, 129, 319-332.
PDB code: 2pff
17360522 L.Buetow, T.K.Smith, A.Dawson, S.Fyffe, and W.N.Hunter (2007).
Structure and reactivity of LpxD, the N-acyltransferase of lipid A biosynthesis.
  Proc Natl Acad Sci U S A, 104, 4321-4326.
PDB codes: 2iu8 2iu9 2iua
17431182 M.Leibundgut, S.Jenni, C.Frick, and N.Ban (2007).
Structural basis for substrate delivery by acyl carrier protein in the yeast fatty acid synthase.
  Science, 316, 288-290.
PDB code: 2uv8
17522044 N.R.De Lay, and J.E.Cronan (2007).
In vivo functional analyses of the type II acyl carrier proteins of fatty acid biosynthesis.
  J Biol Chem, 282, 20319-20328.  
16632253 E.J.Drake, D.A.Nicolai, and A.M.Gulick (2006).
Structure of the EntB multidomain nonribosomal peptide synthetase and functional analysis of its interaction with the EntE adenylation domain.
  Chem Biol, 13, 409-419.
PDB code: 2fq1
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.  
16597827 M.A.Johnson, W.Peti, T.Herrmann, I.A.Wilson, and K.Wüthrich (2006).
Solution structure of Asl1650, an acyl carrier protein from Anabaena sp. PCC 7120 with a variant phosphopantetheinylation-site sequence.
  Protein Sci, 15, 1030-1041.
PDB codes: 2afd 2afe
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.  
16962973 R.M.Van Wagoner, and J.Clardy (2006).
FeeM, an N-acyl amino acid synthase from an uncultured soil microbe: structure, mechanism, and acyl carrier protein binding.
  Structure, 14, 1425-1435.
PDB code: 2g0b
17012233 S.Rafi, P.Novichenok, S.Kolappan, X.Zhang, C.F.Stratton, R.Rawat, C.Kisker, C.Simmerling, and P.J.Tonge (2006).
Structure of acyl carrier protein bound to FabI, the FASII enoyl reductase from Escherichia coli.
  J Biol Chem, 281, 39285-39293.
PDB code: 2fhs
16895912 Y.Huang, E.Wendt-Pienkowski, and B.Shen (2006).
A dedicated phosphopantetheinyl transferase for the fredericamycin polyketide synthase from Streptomyces griseus.
  J Biol Chem, 281, 29660-29668.  
16648134 Y.M.Zhang, S.W.White, and C.O.Rock (2006).
Inhibiting bacterial fatty acid synthesis.
  J Biol Chem, 281, 17541-17544.  
15569690 G.Schmoock, F.Pfennig, J.Jewiarz, W.Schlumbohm, W.Laubinger, F.Schauwecker, and U.Keller (2005).
Functional cross-talk between fatty acid synthesis and nonribosomal peptide synthesis in quinoxaline antibiotic-producing streptomycetes.
  J Biol Chem, 280, 4339-4349.  
16107329 J.Thomas, and J.E.Cronan (2005).
The enigmatic acyl carrier protein phosphodiesterase of Escherichia coli: genetic and enzymological characterization.
  J Biol Chem, 280, 34675-34683.  
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.  
15039582 D.L.Daubaras, E.M.Wilson, T.Black, C.Strickland, B.M.Beyer, and P.Orth (2004).
Crystallization and preliminary X-ray analysis of the acyl carrier protein synthase (AcpS) from Staphylococcus aureus.
  Acta Crystallogr D Biol Crystallogr, 60, 773-774.  
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.  
15306017 T.A.Gould, H.P.Schweizer, and M.E.Churchill (2004).
Structure of the Pseudomonas aeruginosa acyl-homoserinelactone synthase LasI.
  Mol Microbiol, 53, 1135-1146.
PDB code: 1ro5
15333924 X.Qiu, and C.A.Janson (2004).
Structure of apo acyl carrier protein and a proposal to engineer protein crystallization through metal ions.
  Acta Crystallogr D Biol Crystallogr, 60, 1545-1554.
PDB code: 1t8k
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.  
14527946 Y.M.Zhang, B.Wu, J.Zheng, and C.O.Rock (2003).
Key residues responsible for acyl carrier protein and beta-ketoacyl-acyl carrier protein reductase (FabG) interaction.
  J Biol Chem, 278, 52935-52943.  
11756461 C.C.Huang, C.V.Smith, M.S.Glickman, W.R.Jacobs, and J.C.Sacchettini (2002).
Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis.
  J Biol Chem, 277, 11559-11569.
PDB codes: 1kp9 1kpg 1kph 1kpi 1l1e
11825906 H.C.Wong, G.Liu, Y.M.Zhang, C.O.Rock, and J.Zheng (2002).
The solution structure of acyl carrier protein from Mycobacterium tuberculosis.
  J Biol Chem, 277, 15874-15880.
PDB code: 1klp
  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.  
11997478 L.E.Kemp, C.S.Bond, and W.N.Hunter (2002).
Structure of 2C-methyl-D-erythritol 2,4- cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development.
  Proc Natl Acad Sci U S A, 99, 6591-6596.
PDB code: 1gx1
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.  
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.  
11525165 G.Y.Xu, A.Tam, L.Lin, J.Hixon, C.C.Fritz, and R.Powers (2001).
Solution structure of B. subtilis acyl carrier protein.
  Structure, 9, 277-287.
PDB code: 1hy8
11544358 J.W.Campbell, and J.E.Cronan (2001).
Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery.
  Annu Rev Microbiol, 55, 305-332.  
11591436 R.J.Heath, S.W.White, and C.O.Rock (2001).
Lipid biosynthesis as a target for antibacterial agents.
  Prog Lipid Res, 40, 467-497.  
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
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.