PDBsum entry 2pff

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Transferase PDB id
Protein chains
1683 a.a.
2006 a.a.
65 a.a.
PDB id:
Name: Transferase
Title: Structural insights of yeast fatty acid synthase
Structure: Fatty acid synthase subunit alpha. Chain: a, d, g. Synonym: includes: acyl carrier. 3-oxoacyl-[acyl-carrier-pr reductase (ec (beta-ketoacyl reductase). 3-oxoac carrier-protein] synthase (ec (beta-ketoacyl synt fatty acid synthase subunit beta. Chain: b, e, h. Synonym: includes: 3- hydroxypalmitoyl-[acyl-carrier-protei dehydratase (ec Enoyl-[acyl-carrier-protein] red
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Strain: yit613. Synthetic: yes
4.00Å     R-factor:   0.319     R-free:   0.346
Authors: Y.Xiong,I.B.Lomakin,T.A.Steitz
Key ref:
I.B.Lomakin et al. (2007). The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together. Cell, 129, 319-332. PubMed id: 17448991 DOI: 10.1016/j.cell.2007.03.013
04-Apr-07     Release date:   10-Jul-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P19097  (FAS2_YEAST) -  Fatty acid synthase subunit alpha
1887 a.a.
1683 a.a.*
Protein chains
Pfam   ArchSchema ?
P07149  (FAS1_YEAST) -  Fatty acid synthase subunit beta
2051 a.a.
2006 a.a.*
Protein chains
No UniProt id for this chain
Struc: 65 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1802 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 2: Chains A, D, G: E.C.  - 3-oxoacyl-[acyl-carrier-protein] reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP+ = 3-oxoacyl-[acyl- carrier-protein] + NADPH
+ NADP(+)
= 3-oxoacyl-[acyl- carrier-protein]
   Enzyme class 3: Chains A, D, G: E.C.  - Beta-ketoacyl-[acyl-carrier-protein] synthase I.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = 3-oxoacyl- [acyl-carrier-protein] + CO2 + [acyl-carrier-protein]
+ malonyl-[acyl-carrier-protein]
= 3-oxoacyl- [acyl-carrier-protein]
+ CO(2)
+ [acyl-carrier-protein]
   Enzyme class 4: Chains A, B, D, E, G, H: E.C.  - Fatty-acyl-CoA synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + n malonyl-CoA + 2n NADPH = long-chain-acyl-CoA + n CoA + n CO2 + 2n NADP+
+ n malonyl-CoA
+ 2n NADPH
= long-chain-acyl-CoA
+ n CoA
+ n CO(2)
+ 2n NADP(+)
   Enzyme class 5: Chains B, E, H: E.C.  - Enoyl-[acyl-carrier-protein] reductase (NADH).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An acyl-[acyl-carrier protein] + NAD+ = a trans-2,3-dehydroacyl-[acyl- carrier protein] + NADH
acyl-[acyl-carrier protein]
+ n NAD(+)
= trans-2,3-dehydroacyl-[acyl- carrier protein]
   Enzyme class 6: Chains B, E, H: E.C.  - [Acyl-carrier-protein] S-acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + [acyl-carrier-protein] = CoA + acetyl-[acyl-carrier- protein]
+ n [acyl-carrier-protein]
= CoA
+ acetyl-[acyl-carrier- protein]
   Enzyme class 7: Chains B, E, H: E.C.  - [Acyl-carrier-protein] S-malonyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Malonyl-CoA + an [acyl-carrier-protein] = CoA + a malonyl-[acyl-carrier- protein]
+ n [acyl-carrier-protein]
= CoA
+ malonyl-[acyl-carrier- protein]
   Enzyme class 8: Chains B, E, H: E.C.  - Oleoyl-[acyl-carrier-protein] hydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Oleoyl-[acyl-carrier-protein] + H2O = [acyl-carrier-protein] + oleate
+ n H(2)O
= [acyl-carrier-protein]
+ oleate
   Enzyme class 9: Chains B, E, H: E.C.  - 3-hydroxyacyl-[acyl-carrier-protein] dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A (3R)-3-hydroxyacyl-[acyl-carrier protein] = a trans-2-enoyl-[acyl- carrier protein] + H2O
(3R)-3-hydroxyacyl-[acyl-carrier protein]
= n trans-2-enoyl-[acyl- carrier protein]
+ H(2)O
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!
  Cellular component     fatty acid synthase complex   1 term 
  Biological process     metabolic process   3 terms 
  Biochemical function     catalytic activity     4 terms  


DOI no: 10.1016/j.cell.2007.03.013 Cell 129:319-332 (2007)
PubMed id: 17448991  
The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together.
I.B.Lomakin, Y.Xiong, T.A.Steitz.
In yeast, the whole metabolic pathway for making 16- and 18-carbon fatty acids is carried out by fatty acid synthase, a 2.6 megadalton molecular-weight macromolecular assembly containing six copies of all eight catalytic centers. We have determined its crystal structure, which illuminates how this enzyme is initially activated and then carries out multiple steps of synthesis in each of six sterically isolated reaction chambers. Six of the catalytic sites are in the wall of the assembly facing an acyl carrier protein (ACP) bound to the ketoacyl synthase domain. Two-dimensional diffusion of substrates to the catalytic sites may be achieved by the electrostatically negative ACP swinging to each of the six electrostatically positive catalytic sites. The phosphopantetheinyl transferase domain lies outside the shell of the assembly, inaccessible to ACP that lies inside, suggesting that the attachment of the pantetheine arm to ACP must occur before complete assembly of the complex.
  Selected figure(s)  
Figure 4.
Figure 4. Structure of the β Subunit
(A) Domain organization of the β subunit is shown at the top, a ribbon diagram of the FAS particle without the α subunits on the left, and an individual β subunit on the right.
(B, C, E, and F) Ribbon diagrams of individual domains. Red sticks show side chains of active-site residues.
(B) AT (green), AT helical flap (blue).
(C) MPT (beige), MPT helical flap (blue). The orientation is the same as that of AT.
(D) Composition of the AT active center (pale green). Residues involved in catalysis are shown in red. Malonate (yellow) is modeled into the putative active sites as a reference (from PDB ID code 2G2Z).
(E) ER (blue) with the FMN molecule (green) in the active site.
(F) DHn (light blue) and DHc (cyan) form a pseudodimer (DH domain).
Figure 6.
Figure 6. ACP Interactions with Electrostatically Complementary Active Sites
(A) Surface electrostatic potential representations (blue for positive charge, red for negative charge) shown for KR (top left), AT (top center), MPT (top right), KS/KS dimer (bottom left), and ACP (bottom center). Active centers are shown in yellow.
(B) Surface representation of the α subunit domain 1 (ACP subdomain in gray-green, C-terminal helical subdomain in green) bound to the KS/KS dimer (blue) and the “hub” (pink).
  The above figures are reprinted by permission from Cell Press: Cell (2007, 129, 319-332) copyright 2007.  
  Figures were 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
21152407 C.W.Pemble, P.K.Mehta, S.Mehra, Z.Li, A.Nourse, R.E.Lee, and S.W.White (2010).
Crystal structure of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase•dihydropteroate synthase bifunctional enzyme from Francisella tularensis.
  PLoS One, 5, e14165.
PDB codes: 3mcm 3mcn 3mco
20662770 D.I.Chan, and H.J.Vogel (2010).
Current understanding of fatty acid biosynthesis and the acyl carrier protein.
  Biochem J, 430, 1.  
20014832 G.A.Zornetzer, J.Tanem, B.G.Fox, and J.L.Markley (2010).
The length of the bound fatty acid influences the dynamics of the acyl carrier protein and the stability of the thioester bond.
  Biochemistry, 49, 470-477.  
20231485 P.Gipson, D.J.Mills, R.Wouts, M.Grininger, J.Vonck, and W.Kühlbrandt (2010).
Direct structural insight into the substrate-shuttling mechanism of yeast fatty acid synthase by electron cryomicroscopy.
  Proc Natl Acad Sci U S A, 107, 9164-9169.  
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.  
20189105 W.Mattheus, L.J.Gao, P.Herdewijn, B.Landuyt, J.Verhaegen, J.Masschelein, G.Volckaert, and R.Lavigne (2010).
Isolation and purification of a new kalimantacin/batumin-related polyketide antibiotic and elucidation of its biosynthesis gene cluster.
  Chem Biol, 17, 149-159.  
20336235 Z.X.Liang (2010).
Complexity and simplicity in the biosynthesis of enediyne natural products.
  Nat Prod Rep, 27, 499-528.  
19620981 A.Horie, T.Tomita, A.Saiki, H.Kono, H.Taka, R.Mineki, T.Fujimura, C.Nishiyama, T.Kuzuyama, and M.Nishiyama (2009).
Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus.
  Nat Chem Biol, 5, 673-679.  
19151726 E.J.Brignole, S.Smith, and F.J.Asturias (2009).
Conformational flexibility of metazoan fatty acid synthase enables catalysis.
  Nat Struct Mol Biol, 16, 190-197.  
19549604 G.Bunkoczi, S.Misquitta, X.Wu, W.H.Lee, A.Rojkova, G.Kochan, K.L.Kavanagh, U.Oppermann, and S.Smith (2009).
Structural basis for different specificities of acyltransferases associated with the human cytosolic and mitochondrial fatty acid synthases.
  Chem Biol, 16, 667-675.
PDB codes: 2c2n 2jfd
19151923 R.P.Massengo-Tiassé, and J.E.Cronan (2009).
Diversity in enoyl-acyl carrier protein reductases.
  Cell Mol Life Sci, 66, 1507-1517.  
19171964 S.Jenni, and N.Ban (2009).
Imperfect pseudo-merohedral twinning in crystals of fungal fatty acid synthase.
  Acta Crystallogr D Biol Crystallogr, 65, 101-111.  
18199837 A.Miyanaga, N.Funa, T.Awakawa, and S.Horinouchi (2008).
Direct transfer of starter substrates from type I fatty acid synthase to type III polyketide synthases in phenolic lipid synthesis.
  Proc Natl Acad Sci U S A, 105, 871-876.  
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
17971456 E.Płoskoń, C.J.Arthur, S.E.Evans, C.Williams, J.Crosby, T.J.Simpson, and M.P.Crump (2008).
A mammalian type I fatty acid synthase acyl carrier protein domain does not sequester acyl chains.
  J Biol Chem, 283, 518-528.
PDB code: 2png
18551496 J.M.Crawford, A.L.Vagstad, K.C.Ehrlich, D.W.Udwary, and C.A.Townsend (2008).
Acyl-carrier protein-phosphopantetheinyltransferase partnerships in fungal fatty acid synthases.
  Chembiochem, 9, 1559-1563.  
18223152 J.Zhang, S.G.Van Lanen, J.Ju, W.Liu, P.C.Dorrestein, W.Li, N.L.Kelleher, and B.Shen (2008).
A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis.
  Proc Natl Acad Sci U S A, 105, 1460-1465.  
18357594 K.J.Weissman, and R.Müller (2008).
Protein-protein interactions in multienzyme megasynthetases.
  Chembiochem, 9, 826-848.  
19021139 L.Betancor, M.J.Fernández, K.J.Weissman, and P.F.Leadlay (2008).
Improved catalytic activity of a purified multienzyme from a modular polyketide synthase after coexpression with Streptomyces chaperonins in Escherichia coli.
  Chembiochem, 9, 2962-2966.  
18312417 M.J.Vázquez, W.Leavens, R.Liu, B.Rodríguez, M.Read, S.Richards, D.Winegar, and J.M.Domínguez (2008).
Discovery of GSK837149A, an inhibitor of human fatty acid synthase targeting the beta-ketoacyl reductase reaction.
  FEBS J, 275, 1556-1567.  
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.  
18187576 M.Simonović, and T.A.Steitz (2008).
Cross-crystal averaging reveals that the structure of the peptidyl-transferase center is the same in the 70S ribosome and the 50S subunit.
  Proc Natl Acad Sci U S A, 105, 500-505.  
18725634 P.Johansson, B.Wiltschi, P.Kumari, B.Kessler, C.Vonrhein, J.Vonck, D.Oesterhelt, and M.Grininger (2008).
Inhibition of the fungal fatty acid synthase type I multienzyme complex.
  Proc Natl Acad Sci U S A, 105, 12803-12808.
PDB code: 2vkz
18772430 T.Maier, M.Leibundgut, and N.Ban (2008).
The crystal structure of a mammalian fatty acid synthase.
  Science, 321, 1315-1322.
PDB codes: 2vz8 2vz9
18094470 Y.Xiong (2008).
From electron microscopy to X-ray crystallography: molecular-replacement case studies.
  Acta Crystallogr D Biol Crystallogr, 64, 76-82.  
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
17707686 H.T.Wright, and K.A.Reynolds (2007).
Antibacterial targets in fatty acid biosynthesis.
  Curr Opin Microbiol, 10, 447-453.  
17935970 R.S.Gokhale, R.Sankaranarayanan, and D.Mohanty (2007).
Versatility of polyketide synthases in generating metabolic diversity.
  Curr Opin Struct Biol, 17, 736-743.  
18096506 S.Pasta, A.Witkowski, A.K.Joshi, and S.Smith (2007).
Catalytic residues are shared between two pseudosubunits of the dehydratase domain of the animal fatty acid synthase.
  Chem Biol, 14, 1377-1385.  
17898897 S.Smith, and S.C.Tsai (2007).
The type I fatty acid and polyketide synthases: a tale of two megasynthases.
  Nat Prod Rep, 24, 1041-1072.  
17719544 V.Denic, and J.S.Weissman (2007).
A molecular caliper mechanism for determining very long-chain fatty acid length.
  Cell, 130, 663-677.  
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.