PDBsum entry 2byw

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Transferase PDB id
Protein chains
406 a.a. *
NH4 ×8
Waters ×1079
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structure of escherichia coli beta-ketoacyl (acyl carrier protein) synthase i lys328ala mutant
Structure: 3-oxoacyl-[acyl-carrier-protein] synthase i. Chain: a, b, c, d. Synonym: beta-ketoacyl-acp synthase i, kas i. Engineered: yes. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
1.70Å     R-factor:   0.181     R-free:   0.209
Authors: J.G.Olsen,P.Von Wettstein-Knowles,A.Henriksen
Key ref:
P.von Wettstein-Knowles et al. (2006). Fatty acid synthesis. FEBS J, 273, 695-710. PubMed id: 16441657 DOI: 10.1111/j.1742-4658.2005.05101.x
09-Aug-05     Release date:   09-Sep-05    
Supersedes: 1oeq
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0A953  (FABB_ECOLI) -  3-oxoacyl-[acyl-carrier-protein] synthase 1
406 a.a.
406 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: 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]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     4 terms  


DOI no: 10.1111/j.1742-4658.2005.05101.x FEBS J 273:695-710 (2006)
PubMed id: 16441657  
Fatty acid synthesis.
P.von Wettstein-Knowles, J.G.Olsen, K.A.McGuire, A.Henriksen.
beta-Ketoacyl-acyl carrier protein (ACP) synthase enzymes join short carbon units to construct fatty acyl chains by a three-step Claisen condensation reaction. The reaction starts with a trans thioesterification of the acyl primer substrate from ACP to the enzyme. Subsequently, the donor substrate malonyl-ACP is decarboxylated to form a carbanion intermediate, which in the third step attacks C1 of the primer substrate giving rise to an elongated acyl chain. A subgroup of beta-ketoacyl-ACP synthases, including mitochondrial beta-ketoacyl-ACP synthase, bacterial plus plastid beta-ketoacyl-ACP synthases I and II, and a domain of human fatty acid synthase, have a Cys-His-His triad and also a completely conserved Lys in the active site. To examine the role of these residues in catalysis, H298Q, H298E and six K328 mutants of Escherichia colibeta-ketoacyl-ACP synthase I were constructed and their ability to carry out the trans thioesterification, decarboxylation and/or condensation steps of the reaction was ascertained. The crystal structures of wild-type and eight mutant enzymes with and/or without bound substrate were determined. The H298E enzyme shows residual decarboxylase activity in the pH range 6-8, whereas the H298Q enzyme appears to be completely decarboxylation deficient, showing that H298 serves as a catalytic base in the decarboxylation step. Lys328 has a dual role in catalysis: its charge influences acyl transfer to the active site Cys, and the steric restraint imposed on H333 is of critical importance for decarboxylation activity. This restraint makes H333 an obligate hydrogen bond donor at N(epsilon), directed only towards the active site and malonyl-ACP binding area in the fatty acid complex.
  Selected figure(s)  
Figure 1.
Fig. 1. Superimposition of the KAS I C163S-C12 (white, light colors) [3] and KAS I–C8 (gray, dark colors) active sites. Red spheres are water molecules. Blue atoms represent nitrogen, red represent oxygen, and green represents sulfur. Figures 1, 2 and 4 are made in MOLSCRIPT[41].
Figure 3.
Fig. 3. The active sites of the wild-type KAS I, its H298 mutants and their acyl complexes. (A) Wild-type. (B) WT–C8. (C) Superimposition of the wild-type (white, light colors) and H298E (orange, dark colors). (D) H298E. (E) H298E–C12. (F) H298Q. (G) H298Q–C12. (H) Superimposition of H298Q and H298Q–C12. In (A, B) and (D–G), water molecules (red spheres) within hydrogen bonding distance are indicated with dashed lines. (H) Superimposition of H298Q (orange, dark colors) and H298Q–C12 (white, light colors) not including water molecules. Figure prepared using PYMOL[42].
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS J (2006, 273, 695-710) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
17242430 C.E.Christensen, B.B.Kragelund, P.von Wettstein-Knowles, and A.Henriksen (2007).
Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase.
  Protein Sci, 16, 261-272.
PDB codes: 2iwy 2iwz 2ix4
17328673 C.Khosla, Y.Tang, A.Y.Chen, N.A.Schnarr, and D.E.Cane (2007).
Structure and mechanism of the 6-deoxyerythronolide B synthase.
  Annu Rev Biochem, 76, 195-221.  
17431182 M.Leibundgut, S.Jenni, C.Frick, and N.Ban (2007).
Structural basis for substrate delivery by acyl carrier protein in the yeast fatty acid synthase.
  Science, 316, 288-290.
PDB code: 2uv8
17174327 S.Sridharan, L.Wang, A.K.Brown, L.G.Dover, L.Kremer, G.S.Besra, and J.C.Sacchettini (2007).
X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl acyl carrier protein synthase II (mtKasB).
  J Mol Biol, 366, 469-480.
PDB code: 2gp6
17719492 Y.Tang, A.Y.Chen, C.Y.Kim, D.E.Cane, and C.Khosla (2007).
Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase.
  Chem Biol, 14, 931-943.
PDB code: 2qo3
16618705 Y.M.Zhang, J.Hurlbert, S.W.White, and C.O.Rock (2006).
Roles of the active site water, histidine 303, and phenylalanine 396 in the catalytic mechanism of the elongation condensing enzyme of Streptococcus pneumoniae.
  J Biol Chem, 281, 17390-17399.
PDB code: 2alm
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.