PDBsum entry 3hhd

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protein metals Protein-protein interface(s) links
Transferase, hydrolase PDB id
Protein chain
852 a.a. *
_CL ×2
Waters ×1808
* Residue conservation analysis
PDB id:
Name: Transferase, hydrolase
Title: Structure of the human fatty acid synthase ks-mat didomain as a framework for inhibitor design.
Structure: Fatty acid synthase. Chain: a, b, c, d. Fragment: unp residues 2-963. Synonym: [acyl-carrier-protein] s-acetyltransferase, [acyl- carrier-protein] s-malonyltransferase, 3-oxoacyl-[acyl- carrier-protein] synthase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: fasn, fas. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
2.15Å     R-factor:   0.171     R-free:   0.211
Authors: G.M.Pappenberger,J.Benz,R.Thoma,M.G.Rudolph
Key ref: G.Pappenberger et al. (2010). Structure of the human fatty acid synthase KS-MAT didomain as a framework for inhibitor design. J Mol Biol, 397, 508-519. PubMed id: 20132826 DOI: 10.1016/j.jmb.2010.01.066
15-May-09     Release date:   09-Feb-10    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P49327  (FAS_HUMAN) -  Fatty acid synthase
2511 a.a.
852 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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 + an [acyl-carrier-protein] = CoA + a 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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     catalytic activity     2 terms  


DOI no: 10.1016/j.jmb.2010.01.066 J Mol Biol 397:508-519 (2010)
PubMed id: 20132826  
Structure of the human fatty acid synthase KS-MAT didomain as a framework for inhibitor design.
G.Pappenberger, J.Benz, B.Gsell, M.Hennig, A.Ruf, M.Stihle, R.Thoma, M.G.Rudolph.
The human fatty acid synthase (FAS) is a key enzyme in the metabolism of fatty acids and a target for antineoplastic and antiobesity drug development. Due to its size and flexibility, structural studies of mammalian FAS have been limited to individual domains or intermediate-resolution studies of the complete porcine FAS. We describe the high-resolution crystal structure of a large part of human FAS that encompasses the tandem domain of beta-ketoacyl synthase (KS) connected by a linker domain to the malonyltransferase (MAT) domain. Hinge regions that allow for substantial flexibility of the subdomains are defined. The KS domain forms the canonical dimer, and its substrate-binding site geometry differs markedly from that of bacterial homologues but is similar to that of the porcine orthologue. The didomain structure reveals a possible way to generate a small and compact KS domain by omitting a large part of the linker and MAT domains, which could greatly aid in rapid screening of KS inhibitors. In the crystal, the MAT domain exhibits two closed conformations that differ significantly by rigid-body plasticity. This flexibility may be important for catalysis and extends the conformational space previously known for type I FAS and 6-deoxyerythronolide B synthase.

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.  
  20706604 H.Liu, J.Y.Liu, X.Wu, and J.T.Zhang (2010).
Biochemistry, molecular biology, and pharmacology of fatty acid synthase, an emerging therapeutic target and diagnosis/prognosis marker.
  Int J Biochem Mol Biol, 1, 69-89.  
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