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PDBsum entry 2iwy

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protein ligands Protein-protein interface(s) links
Transferase PDB id
2iwy
Jmol
Contents
Protein chain
420 a.a. *
Ligands
NH4 ×2
Waters ×410
* Residue conservation analysis
PDB id:
2iwy
Name: Transferase
Title: Human mitochondrial beta-ketoacyl acp synthase
Structure: 3-oxoacyl-[acyl-carrier-protein] synthase. Chain: a, b. Fragment: residues 38-459. Synonym: beta-ketoacyl synthase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: m15(prep4). Other_details: sumio sugano, university of tokyo
Resolution:
2.06Å     R-factor:   0.163     R-free:   0.205
Authors: C.E.Christensen,B.B.Kragelund,P.Von Wettstein-Knowles, A.Hen
Key ref:
C.E.Christensen et al. (2007). Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase. Protein Sci, 16, 261-272. PubMed id: 17242430 DOI: 10.1110/ps.062473707
Date:
05-Jul-06     Release date:   06-Feb-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9NWU1  (OXSM_HUMAN) -  3-oxoacyl-[acyl-carrier-protein] synthase, mitochondrial
Seq:
Struc:
459 a.a.
420 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: 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]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   1 term 
  Biological process     metabolic process   7 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1110/ps.062473707 Protein Sci 16:261-272 (2007)
PubMed id: 17242430  
 
 
Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase.
C.E.Christensen, B.B.Kragelund, P.von Wettstein-Knowles, A.Henriksen.
 
  ABSTRACT  
 
Two distinct ways of organizing fatty acid biosynthesis exist: the multifunctional type I fatty acid synthase (FAS) of mammals, fungi, and lower eukaryotes with activities residing on one or two polypeptides; and the dissociated type II FAS of prokaryotes, plastids, and mitochondria with individual activities encoded by discrete genes. The beta-ketoacyl [ACP] synthase (KAS) moiety of the mitochondrial FAS (mtKAS) is targeted by the antibiotic cerulenin and possibly by the other antibiotics inhibiting prokaryotic KASes: thiolactomycin, platensimycin, and the alpha-methylene butyrolactone, C75. The high degree of structural similarity between mitochondrial and prokaryotic KASes complicates development of novel antibiotics targeting prokaryotic KAS without affecting KAS domains of cytoplasmic FAS. KASes catalyze the C(2) fatty acid elongation reaction using either a Cys-His-His or Cys-His-Asn catalytic triad. Three KASes with different substrate specificities participate in synthesis of the C(16) and C(18) products of prokaryotic FAS. By comparison, mtKAS carries out all elongation reactions in the mitochondria. We present the X-ray crystal structures of the Cys-His-His-containing human mtKAS and its hexanoyl complex plus the hexanoyl complex of the plant mtKAS from Arabidopsis thaliana. The structures explain (1) the bimodal (C(6) and C(10)-C(12)) substrate preferences leading to the C(8) lipoic acid precursor and long chains for the membranes, respectively, and (2) the low cerulenin sensitivity of the human enzyme; and (3) reveal two different potential acyl-binding-pocket extensions. Rearrangements taking place in the active site, including subtle changes in the water network, indicate a change in cooperativity of the active-site histidines upon primer binding.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Ca RMSDs between (A) HsmtKAS and HsmtKAS:C6 and (B) AtmtKAS and AtmtKAS:C6. The tube diameter is
Figure 4.
Figure 4. Stereoviews of the HsmtKAS active site. (A) C6 in the acyl-binding pocket. Balls and sticks are colored according to atom
 
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2007, 16, 261-272) copyright 2007.  
  Figures were selected by an automated process.  

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.  
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.  
  19130444 K.C.Nicolaou, J.S.Chen, D.J.Edmonds, and A.A.Estrada (2009).
Recent advances in the chemistry and biology of naturally occurring antibiotics.
  Angew Chem Int Ed Engl, 48, 660-719.  
  18453702 B.Bagautdinov, Y.Ukita, M.Miyano, and N.Kunishima (2008).
Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 358-366.
PDB code: 1j3n
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
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 code is shown on the right.