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PDBsum entry 2cg5

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protein ligands metals Protein-protein interface(s) links
Transferase/hydrolase PDB id
2cg5
Jmol
Contents
Protein chains
266 a.a. *
71 a.a. *
Ligands
COA
PO4
Metals
_MG ×2
_NI
Waters ×24
* Residue conservation analysis
PDB id:
2cg5
Name: Transferase/hydrolase
Title: Structure of aminoadipate-semialdehyde dehydrogenase- phosphopantetheinyl transferase in complex with cytosolic acyl carrier protein and coenzyme a
Structure: L-aminoadipate-semialdehyde dehydrogenase- phosphopantetheinyl transferase. Chain: a. Synonym: 4'-phosphopantetheinyl transferase, alpha- aminoad semialdehyde dehydrogenase- phosphopantetheinyl transferas aasd-ppt, lys5 ortholog. Engineered: yes. Fatty acid synthase. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_cell_line: de3. Expressed in: escherichia coli
Biol. unit: Dimer (from PDB file)
Resolution:
2.70Å     R-factor:   0.195     R-free:   0.247
Authors: G.Bunkoczi,A.Joshi,E.Papagrigoriu,C.Arrowsmith,A.Edwards,M.S J.Weigelt,F.Von Delft,S.Smith,U.Oppermann
Key ref: G.Bunkoczi et al. (2007). Mechanism and substrate recognition of human holo ACP synthase. Chem Biol, 14, 1243-1253. PubMed id: 18022563
Date:
27-Feb-06     Release date:   01-Mar-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9NRN7  (ADPPT_HUMAN) -  L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase
Seq:
Struc:
309 a.a.
266 a.a.*
Protein chain
Pfam   ArchSchema ?
P49327  (FAS_HUMAN) -  Fatty acid synthase
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2511 a.a.
71 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: Chain B: 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 59.00% similarity
= 3-oxoacyl-[acyl- carrier-protein]
+ NADPH
   Enzyme class 2: Chain B: E.C.1.3.1.39  - 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(+)
Bound ligand (Het Group name = COA)
matches with 59.00% similarity
= trans-2,3-dehydroacyl-[acyl- carrier protein]
+ NADPH
   Enzyme class 3: Chain B: E.C.2.3.1.38  - [Acyl-carrier-protein] S-acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + [acyl-carrier-protein] = CoA + acetyl-[acyl-carrier- protein]
Acetyl-CoA
Bound ligand (Het Group name = COA)
matches with 74.00% similarity
+ [acyl-carrier-protein]
= CoA
+ acetyl-[acyl-carrier- protein]
   Enzyme class 4: Chain B: E.C.2.3.1.39  - [Acyl-carrier-protein] S-malonyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Malonyl-CoA + an [acyl-carrier-protein] = CoA + a malonyl-[acyl-carrier- protein]
Malonyl-CoA
Bound ligand (Het Group name = COA)
matches with 70.00% similarity
+ [acyl-carrier-protein]
= CoA
+ malonyl-[acyl-carrier- protein]
   Enzyme class 5: Chain B: 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 6: Chain B: E.C.2.3.1.85  - 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+
Acetyl-CoA
Bound ligand (Het Group name = COA)
matches with 74.00% similarity
+ n malonyl-CoA
+ 2n NADPH
= long-chain fatty acid
+ (n+1) CoA
+ n CO(2)
+ 2n NADP(+)
   Enzyme class 7: Chain B: E.C.3.1.2.14  - Oleoyl-[acyl-carrier-protein] hydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Oleoyl-[acyl-carrier-protein] + H2O = [acyl-carrier-protein] + oleate
Oleoyl-[acyl-carrier-protein]
+ n H(2)O
= [acyl-carrier-protein]
+ oleate
   Enzyme class 8: Chain B: E.C.4.2.1.59  - 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     cytoplasm   3 terms 
  Biological process     small molecule metabolic process   5 terms 
  Biochemical function     protein binding     5 terms  

 

 
    reference    
 
 
Chem Biol 14:1243-1253 (2007)
PubMed id: 18022563  
 
 
Mechanism and substrate recognition of human holo ACP synthase.
G.Bunkoczi, S.Pasta, A.Joshi, X.Wu, K.L.Kavanagh, S.Smith, U.Oppermann.
 
  ABSTRACT  
 
Mammals utilize a single phosphopantetheinyl transferase for the posttranslational modification of at least three different apoproteins: the carrier protein components of cytosolic and mitochondrial fatty acid synthases and the aminoadipate semialdehyde reductase involved in lysine degradation. We determined the crystal structure of the human phosphopantetheinyl transferase, a eukaryotic phosphopantetheinyl transferase characterized, complexed with CoA and Mg(2+), and in ternary complex with CoA and ACP. The involvement of key residues in ligand binding and catalysis was confirmed by mutagenesis and kinetic analysis. Human phosphopantetheinyl transferase exhibits an alpha/beta fold and 2-fold pseudosymmetry similar to the Sfp phosphopantetheinyl transferase from Bacillus subtilis. Although the bound ACP exhibits a typical four-helix structure, its binding is unusual in that it is facilitated predominantly by hydrophobic interactions. A detailed mechanism is proposed describing the substrate binding and catalytic 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.  
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.  
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.  
19170545 J.Cao, H.Xu, H.Zhao, W.Gong, and D.Dunaway-Mariano (2009).
The mechanisms of human hotdog-fold thioesterase 2 (hTHEM2) substrate recognition and catalysis illuminated by a structure and function based analysis.
  Biochemistry, 48, 1293-1304.
PDB code: 3f5o
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.