PDBsum entry 2png

Go to PDB code: 
protein links
Transferase PDB id
Protein chain
89 a.a. *
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Type i rat fatty acid synthase acyl carrier protein (acp) domain
Structure: Fatty acid synthase (ec Chain: a. Fragment: residues 2114-2202, acyl carrier protein. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: fasn. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 30 models
Authors: E.A.Ploskon,C.J.Arthur,S.E.Evans,C.Williams,J.Crosby, M.P.Crump
Key ref:
E.Płoskoń et al. (2008). A mammalian type I fatty acid synthase acyl carrier protein domain does not sequester acyl chains. J Biol Chem, 283, 518-528. PubMed id: 17971456 DOI: 10.1074/jbc.M703454200
24-Apr-07     Release date:   05-Jun-07    
Supersedes: 1n8l
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P12785  (FAS_RAT) -  Fatty acid synthase
2505 a.a.
89 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: 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 2: E.C.  - Enoyl-[acyl-carrier-protein] reductase (Nadph, Re-specific).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An acyl-[acyl-carrier protein] + NADP+ = a trans-2,3-dehydroacyl-[acyl- carrier protein] + NADPH
acyl-[acyl-carrier protein]
+ NADP(+)
= trans-2,3-dehydroacyl-[acyl- carrier protein]
   Enzyme class 3: E.C.  - [Acyl-carrier-protein] S-acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + [acyl-carrier-protein] = CoA + acetyl-[acyl-carrier- protein]
+ [acyl-carrier-protein]
= CoA
+ acetyl-[acyl-carrier- protein]
   Enzyme class 4: E.C.  - [Acyl-carrier-protein] S-malonyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Malonyl-CoA + [acyl-carrier-protein] = CoA + malonyl-[acyl-carrier- protein]
+ [acyl-carrier-protein]
= CoA
+ malonyl-[acyl-carrier- protein]
   Enzyme class 5: 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 6: E.C.  - Fatty-acid synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + n malonyl-CoA + 2n NADPH = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+
+ n malonyl-CoA
+ 2n NADPH
= long-chain fatty acid
+ (n+1) CoA
+ n CO(2)
+ 2n NADP(+)
   Enzyme class 7: 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 8: 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


DOI no: 10.1074/jbc.M703454200 J Biol Chem 283:518-528 (2008)
PubMed id: 17971456  
A mammalian type I fatty acid synthase acyl carrier protein domain does not sequester acyl chains.
E.Płoskoń, C.J.Arthur, S.E.Evans, C.Williams, J.Crosby, T.J.Simpson, M.P.Crump.
The synthases that produce fatty acids in mammals (FASs) are arranged as large multidomain polypeptides. The growing fatty acid chain is bound covalently during chain elongation and reduction to the acyl carrier protein (ACP) domain that is then able to access each catalytic site. In this work we report the high-resolution nuclear magnetic resonance (NMR) solution structure of the isolated rat fatty acid synthase apoACP domain. The final ensemble of NMR structures and backbone (15)N relaxation studies show that apoACP adopts a single, well defined fold. On conversion to the holo form, several small chemical shift changes are observed on the ACP for residues surrounding the phosphopantetheine attachment site (as monitored by backbone (1)H-(15)N correlation experiments). However, there are negligible chemical shift changes when the holo form is modified to either the hexanoyl or palmitoyl forms. For further NMR analysis, a (13)C,(15)N-labeled hexanoyl-ACP sample was prepared and full chemical shift assignments completed. Analysis of two-dimensional F(2)-filtered and three-dimensional (13)C-edited nuclear Overhauser effect spectroscopy experiments revealed no detectable NOEs to the acyl chain. These experiments demonstrate that unlike other FAS ACPs studied, this Type I ACP does not sequester a covalently linked acyl moiety, although transient interactions cannot be ruled out. This is an important mechanistic difference between the ACPs from Type I and Type II FASs and may be significant for the modulation and regulation of these important mega-synthases.
  Selected figure(s)  
Figure 1.
FIGURE 1. A, ensemble of 30 rat FAS ACP structures. Average structures of both the new (B) and old (C) rat FAS apoACP structures. All structures are shown in the same orientation with helix II to the front left and the phosphopantetheine attachment site Ser^38 at the bottom of helix II. C and N termini and helices are labeled.
Figure 6.
FIGURE 6. Comparison of Type I and Type II ACPs. A, the rat FAS apoACP model has been oriented so the loop region between helix I and II points toward the reader. The loop adopts a fold (outlined by a box) that places it in close proximity to the region between helices II and III. Panel B shows an alternate view and expansion of this region that illustrates how the positioning of the loop and the conserved hydrophobic triad (Leu^2144, Leu^2149, and Val^2174) occludes the entrance to a potential acyl chain binding site. The homologous position to that shown in A and B is boxed out in the Type II E. coli FAS ACP (C), B. subtilis FAS ACP (D), and S. cerevisiae fungal FAS ACP (E). The gray arrows show the movement of the loop away from helix III such that the acyl chain binding site is no longer occluded in these ACPs.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 518-528) copyright 2008.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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.  
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.  
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.  
20578000 M.C.Raman, K.A.Johnson, D.J.Clarke, J.H.Naismith, and D.J.Campopiano (2010).
The serine palmitoyltransferase from Sphingomonas wittichii RW1: An interesting link to an unusual acyl carrier protein.
  Biopolymers, 93, 811-822.
PDB code: 2x8u
21127271 S.Kapur, A.Y.Chen, D.E.Cane, and C.Khosla (2010).
Molecular recognition between ketosynthase and acyl carrier protein domains of the 6-deoxyerythronolide B synthase.
  Proc Natl Acad Sci U S A, 107, 22066-22071.  
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.  
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.  
19151923 R.P.Massengo-Tiassé, and J.E.Cronan (2009).
Diversity in enoyl-acyl carrier protein reductases.
  Cell Mol Life Sci, 66, 1507-1517.  
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.  
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.  
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
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
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.