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PDBsum entry 2uvc

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protein ligands Protein-protein interface(s) links
Transferase PDB id
2uvc
Jmol
Contents
Protein chains
(+ 0 more) 2060 a.a. *
Ligands
FMN ×6
NAP ×6
* Residue conservation analysis
PDB id:
2uvc
Name: Transferase
Title: Crystal structure of fatty acid synthase complexed with NADP+ from thermomyces lanuginosus at 3.1 angstrom resolution. This file contains the beta subunits of the fatty acid synthase. The entire crystal structure consists of one heterododecameric fatty acid synthase and is described in remark 400
Structure: Fatty acid synthase beta subunits. Chain: g, h, i, j, k, l
Source: Thermomyces lanuginosus. Organism_taxid: 5541. Other_details: dsmz10635
Resolution:
3.10Å     R-factor:   0.270     R-free:   0.300
Authors: S.Jenni,M.Leibundgut,D.Boehringer,C.Frick,B.Mikolasek,N.Ban
Key ref:
S.Jenni et al. (2007). Structure of fungal fatty acid synthase and implications for iterative substrate shuttling. Science, 316, 254-261. PubMed id: 17431175 DOI: 10.1126/science.1138248
Date:
09-Mar-07     Release date:   17-Apr-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
No UniProt id for this chain
Struc:  
Struc:  
Struc:  
Struc:  
Struc: 2060 a.a.
Key:    Secondary structure  CATH domain

 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     5 terms  

 

 
DOI no: 10.1126/science.1138248 Science 316:254-261 (2007)
PubMed id: 17431175  
 
 
Structure of fungal fatty acid synthase and implications for iterative substrate shuttling.
S.Jenni, M.Leibundgut, D.Boehringer, C.Frick, B.Mikolásek, N.Ban.
 
  ABSTRACT  
 
We report crystal structures of the 2.6-megadalton alpha6beta6 heterododecameric fatty acid synthase from Thermomyces lanuginosus at 3.1 angstrom resolution. The alpha and beta polypeptide chains form the six catalytic domains required for fatty acid synthesis and numerous expansion segments responsible for extensive intersubunit connections. Detailed views of all active sites provide insights into substrate specificities and catalytic mechanisms and reveal their unique characteristics, which are due to the integration into the multienzyme. The mode of acyl carrier protein attachment in the reaction chamber, together with the spatial distribution of active sites, suggests that iterative substrate shuttling is achieved by a relatively restricted circular motion of the carrier domain in the multifunctional enzyme.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Structure of the fungal FAS. (A) A ribbon representation of the refined T. lanuginosus FAS structure is shown in two side views along the two-fold axis of symmetry (left and middle) and in a top view along the three-fold axis of symmetry (right). Helices belonging to the central wheel are colored red, helices of the capping domes are shown in green, ß strands are colored blue. The particle has an approximate height and width of 270 Å by 250 Å. "Windows" in the side walls and at the top of the particle are labeled as openings 1 to 5, connections between the dome and the central disk as C1, C2, and C3. (B) Quaternary structure and subunit distribution of the FAS complex. The heterododecameric complex is composed of a D[3]-symmetrical [6] hexamer (subunits are colored pink and blue) and two C[3]-symmetrical ß[3] trimers (subunits are colored green, yellow and gray). In the side view (left), the ß[3] trimers have been moved away from the chains as indicated by the arrows.
Figure 6.
Fig. 6. Substrate shuttling in the fungal FAS. (A) On the basis of the shortest distances between both ACP anchor points (green) and all catalytic domains in the reaction chamber, acompleteset of catalytic sites necessary for the cyclic reaction can be defined (red). On accountofthe elasticity of linkers (yellow), free diffusion of ACP (cyan) would be "channeled" into a circular path, which further increases the local concentration of the ACP in the area where active sites are distributed (arrow). (B) The reaction chamber contains three complete sets of active sites, which are arranged in an approximate plane around the peripheral ACP anchors. Note that different (pink, blue) and ß chains (green, yellow, gray) contribute to each catalytic set.
 
  The above figures are reprinted by permission from the AAAs: Science (2007, 316, 254-261) copyright 2007.  
  Figures were selected by the author.  

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
21292977 B.Wörsdörfer, K.J.Woycechowsky, and D.Hilvert (2011).
Directed evolution of a protein container.
  Science, 331, 589-592.  
20662770 D.I.Chan, and H.J.Vogel (2010).
Current understanding of fatty acid biosynthesis and the acyl carrier protein.
  Biochem J, 430, 1.  
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.  
20332208 T.P.Korman, J.M.Crawford, J.W.Labonte, A.G.Newman, J.Wong, C.A.Townsend, and S.C.Tsai (2010).
Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis.
  Proc Natl Acad Sci U S A, 107, 6246-6251.
PDB code: 3ils
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.  
19636447 A.Koglin, and C.T.Walsh (2009).
Structural insights into nonribosomal peptide enzymatic assembly lines.
  Nat Prod Rep, 26, 987.  
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
19551180 J.L.Meier, and M.D.Burkart (2009).
The chemical biology of modular biosynthetic enzymes.
  Chem Soc Rev, 38, 2012-2045.  
19473548 L.S.Pidugu, K.Maity, K.Ramaswamy, N.Surolia, and K.Suguna (2009).
Analysis of proteins with the 'hot dog' fold: prediction of function and identification of catalytic residues of hypothetical proteins.
  BMC Struct Biol, 9, 37.  
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.  
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
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.  
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.  
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
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.  
18305197 J.Saito, M.Yamada, T.Watanabe, M.Iida, H.Kitagawa, S.Takahata, T.Ozawa, Y.Takeuchi, and F.Ohsawa (2008).
Crystal structure of enoyl-acyl carrier protein reductase (FabK) from Streptococcus pneumoniae reveals the binding mode of an inhibitor.
  Protein Sci, 17, 691-699.
PDB codes: 2z6i 2z6j
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.  
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.  
19172747 M.Sutter, D.Boehringer, S.Gutmann, S.Günther, D.Prangishvili, M.J.Loessner, K.O.Stetter, E.Weber-Ban, and N.Ban (2008).
Structural basis of enzyme encapsulation into a bacterial nanocompartment.
  Nat Struct Mol Biol, 15, 939-947.
PDB code: 3dkt
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
18704072 S.Kapur, and C.Khosla (2008).
Biochemistry: Fit for an enzyme.
  Nature, 454, 832-833.  
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
18412189 T.Moriguchi, Y.Ebizuka, and I.Fujii (2008).
Domain-domain interactions in the iterative type I polyketide synthase ATX from Aspergillus terreus.
  Chembiochem, 9, 1207-1212.  
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.  
18033580 N.Dixon, L.S.Wong, T.H.Geerlings, and J.Micklefield (2007).
Cellular targets of natural products.
  Nat Prod Rep, 24, 1288-1310.  
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.