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PDBsum entry 2wat

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
2wat
Jmol
Contents
Protein chains
121 a.a. *
115 a.a. *
Ligands
COA ×5
Metals
_CL ×4
_MG ×5
Waters ×505
* Residue conservation analysis
PDB id:
2wat
Name: Transferase
Title: Structure of the fungal type i fas ppt domain in complex with coa
Structure: 3-oxoacyl-[acyl-carrier-protein] synthase. Chain: a, b, c, d, e, f. Fragment: phosphopantetheine transferase domain, residues 1766-1887. Synonym: fas ppt, beta-ketoacyl reductase, beta-ketoacyl synthase, fatty acid synthase subunit alpha. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: gold.
Resolution:
2.20Å     R-factor:   0.219     R-free:   0.252
Authors: P.Johansson,B.Mulincacci,C.Koestler,M.Grininger
Key ref:
P.Johansson et al. (2009). Multimeric options for the auto-activation of the Saccharomyces cerevisiae FAS type I megasynthase. Structure, 17, 1063-1074. PubMed id: 19679086 DOI: 10.1016/j.str.2009.06.014
Date:
15-Feb-09     Release date:   25-Aug-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P19097  (FAS2_YEAST) -  Fatty acid synthase subunit alpha
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1887 a.a.
121 a.a.
Protein chain
Pfam   ArchSchema ?
P19097  (FAS2_YEAST) -  Fatty acid synthase subunit alpha
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1887 a.a.
115 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains A, B, C, D, E, F: E.C.1.1.1.100  - 3-oxoacyl-[acyl-carrier-protein] reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP+ = 3-oxoacyl-[acyl- carrier-protein] + NADPH
(3R)-3-hydroxyacyl-[acyl-carrier-protein]
+
NADP(+)
Bound ligand (Het Group name = COA)
matches with 52.00% similarity
= 3-oxoacyl-[acyl- carrier-protein]
+ NADPH
   Enzyme class 2: Chains A, B, C, D, E, F: E.C.2.3.1.41  - 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]
Acyl-[acyl-carrier-protein]
+ malonyl-[acyl-carrier-protein]
= 3-oxoacyl- [acyl-carrier-protein]
+ CO(2)
+ [acyl-carrier-protein]
   Enzyme class 3: Chains A, B, C, D, E, F: E.C.2.3.1.86  - 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+
Acetyl-CoA
Bound ligand (Het Group name = COA)
matches with 94.00% similarity
+ n malonyl-CoA
+ 2n NADPH
= long-chain-acyl-CoA
+ n CoA
+ n CO(2)
+ 2n NADP(+)
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!
  Biological process     macromolecule biosynthetic process   2 terms 
  Biochemical function     magnesium ion binding     2 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.str.2009.06.014 Structure 17:1063-1074 (2009)
PubMed id: 19679086  
 
 
Multimeric options for the auto-activation of the Saccharomyces cerevisiae FAS type I megasynthase.
P.Johansson, B.Mulinacci, C.Koestler, R.Vollrath, D.Oesterhelt, M.Grininger.
 
  ABSTRACT  
 
The fungal type I fatty acid synthase (FAS) is a 2.6 MDa multienzyme complex, catalyzing all necessary steps for the synthesis of long acyl chains. To be catalytically competent, the FAS must be activated by a posttranslational modification of the central acyl carrier domain (ACP) by an intrinsic phosphopantetheine transferase (PPT). However, recent X-ray structures of the fungal FAS revealed a barrel-shaped architecture, with PPT located at the outside of the barrel wall, spatially separated from the ACP caged in the inner volume. This separation indicated that the activation has to proceed before the assembly to the mature complex, in a conformation where the ACP and PPT domains can meet. To gain insight into the auto-activation reaction and also into the fungal FAS assembly pathway, we structurally and functionally characterized the Saccharomyces cerevisiae FAS type I PPT as part of the multienzyme protein and as an isolated domain.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Updated Fungal FAS Model
(A) Docking of the high-resolution PPT monomer into the 4 Å maps S. cerevisiae FAS structure. Averaged omit 2Fo-Fc map is contoured at 1σ within 3 Å from the PPT. For orientation, a 20 Å electron microscopy model is shown as an inset (Johansson et al., 2008).
(B) Potential interactions of PPT E1774 as well as the PPT active residues D1772, E1817, and K1821 with K1460 and E1464 on helix α44.
Figure 6.
Figure 6. FAS Type I ACP
(A) Substructure of the FAS complex showing the ACP docked to the KS domain. For illustration of the KS active site, the FAS inhibitor cerulenin is shown in ball representation in red (Johansson et al., 2008). The phosphopantetheine entrance channels are indicated by green arrows, and the ACP docking domains are highlighted by a gray background. For orientation, a 20 Å electron microscopy model is shown as an inset (Johansson et al., 2008).
(B) Superposition of the FAS type I ACP on the E. coli ACP in its apo-form (PDB-code 1T8K). The active serine S36 of the bacterial ACP is shown.
(C) Superposition of the FAS type I PPT (cyan) and ACP (magenta) domains onto the B. subtilis AcpS/ACP complex (PDB-code 1F80) (white).
(D) Grouped structure-based sequence alignment of four fungal FAS type I/HexA ACP domains (magenta colored bar) and a number of pro- and eukaryotic FAS II ACPs (gray bar). S180 is highlighted (star).
 
  The above figures are reprinted by permission from Cell Press: Structure (2009, 17, 1063-1074) copyright 2009.  
  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
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.  
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.