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PDBsum entry 1ek4

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1ek4
Jmol
Contents
Protein chains
406 a.a. *
Ligands
DAO ×4
Waters ×786
* Residue conservation analysis
PDB id:
1ek4
Name: Transferase
Title: Beta-ketoacyl [acyl carrier protein] synthase i in complex with dodecanoic acid to 1.85 resolution
Structure: Beta-ketoacyl [acyl carrier protein] synthase i. Chain: a, b, c, d. Synonym: kas i. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.85Å     R-factor:   0.173     R-free:   0.196
Authors: J.G.Olsen,A.Kadziola,M.Siggaard-Andersen,P.Von Wettstein- Knowles,S.Larsen
Key ref:
J.G.Olsen et al. (2001). Structures of beta-ketoacyl-acyl carrier protein synthase I complexed with fatty acids elucidate its catalytic machinery. Structure, 9, 233-243. PubMed id: 11286890 DOI: 10.1016/S0969-2126(01)00583-4
Date:
06-Mar-00     Release date:   11-Apr-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A953  (FABB_ECOLI) -  3-oxoacyl-[acyl-carrier-protein] synthase 1
Seq:
Struc:
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.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     cytoplasm   2 terms 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(01)00583-4 Structure 9:233-243 (2001)
PubMed id: 11286890  
 
 
Structures of beta-ketoacyl-acyl carrier protein synthase I complexed with fatty acids elucidate its catalytic machinery.
J.G.Olsen, A.Kadziola, P.von Wettstein-Knowles, M.Siggaard-Andersen, S.Larsen.
 
  ABSTRACT  
 
BACKGROUND: beta-ketoacyl-acyl carrier protein synthase (KAS) I is vital for the construction of the unsaturated fatty acid carbon skeletons characterizing E. coli membrane lipids. The new carbon-carbon bonds are created by KAS I in a Claisen condensation performed in a three-step enzymatic reaction. KAS I belongs to the thiolase fold enzymes, of which structures are known for five other enzymes. RESULTS: Structures of the catalytic Cys-Ser KAS I mutant with covalently bound C10 and C12 acyl substrates have been determined to 2.40 and 1.85 A resolution, respectively. The KAS I dimer is not changed by the formation of the complexes but reveals an asymmetric binding of the two substrates bound to the dimer. A detailed model is proposed for the catalysis of KAS I. Of the two histidines required for decarboxylation, one donates a hydrogen bond to the malonyl thioester oxo group, and the other abstracts a proton from the leaving group. CONCLUSIONS: The same mechanism is proposed for KAS II, which also has a Cys-His-His active site triad. Comparison to the active site architectures of other thiolase fold enzymes carrying out a decarboxylation step suggests that chalcone synthase and KAS III with Cys-His-Asn triads use another mechanism in which both the histidine and the asparagine interact with the thioester oxo group. The acyl binding pockets of KAS I and KAS II are so similar that they alone cannot provide the basis for their differences in substrate specificity.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. The Three-Step Mechanism Characterizing the Decarboxylating Claisen Condensing EnzymesThe first step is a trans-thioesterification of the primer substrate. Subsequently, malonyl-ACP gets decarboxylated to give the carbanion, which then attacks C1 of the primer substrate, followed by release of the product, 3-oxoacyl-ACP

 
  The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 233-243) copyright 2001.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21105981 C.N.Shulse, and E.E.Allen (2011).
Diversity and distribution of microbial long-chain fatty acid biosynthetic genes in the marine environment.
  Environ Microbiol, 13, 684-695.  
20018879 C.A.Machutta, G.R.Bommineni, S.R.Luckner, K.Kapilashrami, B.Ruzsicska, C.Simmerling, C.Kisker, and P.J.Tonge (2010).
Slow onset inhibition of bacterial beta-ketoacyl-acyl carrier protein synthases by thiolactomycin.
  J Biol Chem, 285, 6161-6169.  
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.  
19214500 G.R.Zhao, T.Luo, Y.J.Zhou, X.Jiang, B.Qiao, F.M.Yu, and Y.J.Yuan (2009).
fabC of Streptomyces lydicus involvement in the biosynthesis of streptolydigin.
  Appl Microbiol Biotechnol, 83, 305-313.  
18666307 A.S.Worthington, G.H.Hur, J.L.Meier, Q.Cheng, B.S.Moore, and M.D.Burkart (2008).
Probing the compatibility of type II ketosynthase-carrier protein partners.
  Chembiochem, 9, 2096-2103.  
  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
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
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
17827660 F.Kudo, Y.Kasama, T.Hirayama, and T.Eguchi (2007).
Cloning of the pactamycin biosynthetic gene cluster and characterization of a crucial glycosyltransferase prior to a unique cyclopentane ring formation.
  J Antibiot (Tokyo), 60, 492-503.  
18084068 G.Pappenberger, T.Schulz-Gasch, E.Kusznir, F.Müller, and M.Hennig (2007).
Structure-assisted discovery of an aminothiazole derivative as a lead molecule for inhibition of bacterial fatty-acid synthesis.
  Acta Crystallogr D Biol Crystallogr, 63, 1208-1216.
PDB codes: 2vb7 2vb8 2vb9 2vba
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
16356722 A.M.Haapalainen, G.Meriläinen, and R.K.Wierenga (2006).
The thiolase superfamily: condensing enzymes with diverse reaction specificities.
  Trends Biochem Sci, 31, 64-71.  
16710421 J.Wang, S.M.Soisson, K.Young, W.Shoop, S.Kodali, A.Galgoci, R.Painter, G.Parthasarathy, Y.S.Tang, R.Cummings, S.Ha, K.Dorso, M.Motyl, H.Jayasuriya, J.Ondeyka, K.Herath, C.Zhang, L.Hernandez, J.Allocco, A.Basilio, J.R.Tormo, O.Genilloud, F.Vicente, F.Pelaez, L.Colwell, S.H.Lee, B.Michael, T.Felcetto, C.Gill, L.L.Silver, J.D.Hermes, K.Bartizal, J.Barrett, D.Schmatz, J.W.Becker, D.Cully, and S.B.Singh (2006).
Platensimycin is a selective FabF inhibitor with potent antibiotic properties.
  Nature, 441, 358-361.
PDB codes: 2gfv 2gfw 2gfx 2gfy
16441657 P.von Wettstein-Knowles, J.G.Olsen, K.A.McGuire, and A.Henriksen (2006).
Fatty acid synthesis. Role of active site histidines and lysine in Cys-His-His-type beta-ketoacyl-acyl carrier protein synthases.
  FEBS J, 273, 695-710.
PDB codes: 1h4f 2buh 2bui 2byw 2byx 2byy 2byz 2bz3 2bz4
16513975 T.Maier, S.Jenni, and N.Ban (2006).
Architecture of mammalian fatty acid synthase at 4.5 A resolution.
  Science, 311, 1258-1262.
PDB code: 2cf2
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
15668256 L.Zhang, A.K.Joshi, J.Hofmann, E.Schweizer, and S.Smith (2005).
Cloning, expression, and characterization of the human mitochondrial beta-ketoacyl synthase. Complementation of the yeast CEM1 knock-out strain.
  J Biol Chem, 280, 12422-12429.  
15952903 S.W.White, J.Zheng, Y.M.Zhang, and Rock (2005).
The structural biology of type II fatty acid biosynthesis.
  Annu Rev Biochem, 74, 791-831.  
15194690 H.Wang, and J.E.Cronan (2004).
Functional replacement of the FabA and FabB proteins of Escherichia coli fatty acid synthesis by Enterococcus faecalis FabZ and FabF homologues.
  J Biol Chem, 279, 34489-34495.  
14718655 M.Gensheimer, and A.Mushegian (2004).
Chalcone isomerase family and fold: no longer unique to plants.
  Protein Sci, 13, 540-544.  
15286723 R.Sankaranarayanan, P.Saxena, U.B.Marathe, R.S.Gokhale, V.M.Shanmugam, and R.Rukmini (2004).
A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites.
  Nat Struct Mol Biol, 11, 894-900.
PDB codes: 1ted 1tee
14660674 R.Yasuno, P.von Wettstein-Knowles, and H.Wada (2004).
Identification and molecular characterization of the beta-ketoacyl-[acyl carrier protein] synthase component of the Arabidopsis mitochondrial fatty acid synthase.
  J Biol Chem, 279, 8242-8251.  
15052334 Y.J.Lu, Y.M.Zhang, and C.O.Rock (2004).
Product diversity and regulation of type II fatty acid synthases.
  Biochem Cell Biol, 82, 145-155.  
12837788 A.C.Price, C.O.Rock, and S.W.White (2003).
The 1.3-Angstrom-resolution crystal structure of beta-ketoacyl-acyl carrier protein synthase II from Streptococcus pneumoniae.
  J Bacteriol, 185, 4136-4143.
PDB codes: 1ox0 1oxh
  12889743 C.D.Reeves (2003).
The enzymology of combinatorial biosynthesis.
  Crit Rev Biotechnol, 23, 95.  
12866053 J.H.Dawe, C.T.Porter, J.M.Thornton, and A.B.Tabor (2003).
A template search reveals mechanistic similarities and differences in beta-ketoacyl synthases (KAS) and related enzymes.
  Proteins, 52, 427-435.  
12941968 P.Saxena, G.Yadav, D.Mohanty, and R.S.Gokhale (2003).
A new family of type III polyketide synthases in Mycobacterium tuberculosis.
  J Biol Chem, 278, 44780-44790.  
12689621 S.Smith, A.Witkowski, and A.K.Joshi (2003).
Structural and functional organization of the animal fatty acid synthase.
  Prog Lipid Res, 42, 289-317.  
12148534 A.S.Carlsson, S.T.LaBrie, A.J.Kinney, P.von Wettstein-Knowles, and J.Browse (2002).
A KAS2 cDNA complements the phenotypes of the Arabidopsis fab1 mutant that differs in a single residue bordering the substrate binding pocket.
  Plant J, 29, 761-770.  
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.