PDBsum entry 1dd8

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protein Protein-protein interface(s) links
Transferase PDB id
Protein chains
406 a.a. *
Waters ×508
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of beta-ketoacyl-[acyl carrier protein] synthase i from escherichia coli
Structure: Beta-ketoacyl [acyl carrier protein] synthase i. Chain: a, b, c, d. Ec:
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Dimer (from PQS)
2.30Å     R-factor:   0.188     R-free:   0.219
Authors: J.G.Olsen,A.Kadziola,P.Von Wettstein-Knowles,M.Siggaard- Andersen,Y.Lindquist,S.Larsen
Key ref:
J.G.Olsen et al. (1999). The X-ray crystal structure of beta-ketoacyl [acyl carrier protein] synthase I. FEBS Lett, 460, 46-52. PubMed id: 10571059 DOI: 10.1016/S0014-5793(99)01303-4
09-Nov-99     Release date:   18-Nov-99    
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 1 residue position (black cross)

 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: 10.1016/S0014-5793(99)01303-4 FEBS Lett 460:46-52 (1999)
PubMed id: 10571059  
The X-ray crystal structure of beta-ketoacyl [acyl carrier protein] synthase I.
J.G.Olsen, A.Kadziola, P.von Wettstein-Knowles, M.Siggaard-Andersen, Y.Lindquist, S.Larsen.
The crystal structure of the fatty acid elongating enzyme beta-ketoacyl [acyl carrier protein] synthase I (KAS I) from Escherichia coli has been determined to 2.3 A resolution by molecular replacement using the recently solved crystal structure of KAS II as a search model. The crystal contains two independent dimers in the asymmetric unit. KAS I assumes the thiolase alpha(beta)alpha(beta)alpha fold. Electrostatic potential distribution reveals an acyl carrier protein docking site and a presumed substrate binding pocket was detected extending the active site. Both subunits contribute to each substrate binding site in the dimer.
  Selected figure(s)  
Figure 3.
Fig. 3. Ribbon structure of the KAS I dimer as viewed perpendicular to the two-fold axis. Helices and strands are red and blue respectively in the subunit on the right and pink and light blue in the subunit on the left. Active site residues Cys-163, His-298, and His-333 are shown in ball and stick representation. The site on the right is accessible from above the page, the other from below. Notice the well-defined separation of secondary structural elements from the capping domain on top and the thiolase core domain below. Constructed using Molscript [42].
Figure 5.
Fig. 5. Superposition of the active sites and presumed binding pockets of KAS I (dark gray sticks) and KAS II (white sticks) in ball-and-stick representation. KAS I residues are labelled with capital letters and KAS II residues in lower case, those marked with ’ are from the other subunit in the dimer. The Cα of KAS II Ile-108 overlaps with the Cα of KAS I Gly-107, and its side chain points into the cavity in KAS I. The KAS II structural equivalent to KAS I Met-197 is Gly-198. The KAS II equivalent to Gln-113’ is Ile-114’ and the space occupied by Glu-200 is partially filled by Phe-133’. Glu-200 and Gln-113’ are at the bottom of the KAS I cavity. The only polar residue in the KAS II binding pocket is Thr-137’ which is an alanine in KAS I.
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (1999, 460, 46-52) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19550039 M.J.Li, A.Q.Li, H.Xia, C.Z.Zhao, C.S.Li, S.B.Wan, Y.P.Bi, and X.J.Wang (2009).
Cloning and sequence analysis of putative type II fatty acid synthase genes from Arachis hypogaea L.
  J Biosci, 34, 227-238.  
19362634 S.C.Tsai, and B.D.Ames (2009).
Structural enzymology of polyketide synthases.
  Methods Enzymol, 459, 17-47.  
19604480 S.R.Luckner, C.A.Machutta, P.J.Tonge, and C.Kisker (2009).
Crystal structures of Mycobacterium tuberculosis KasA show mode of action within cell wall biosynthesis and its inhibition by thiolactomycin.
  Structure, 17, 1004-1013.
PDB codes: 2wgd 2wge 2wgf 2wgg
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
18219113 G.Parthasarathy, R.Cummings, J.W.Becker, and S.M.Soisson (2008).
Surface-entropy reduction approaches to manipulate crystal forms of beta-ketoacyl acyl carrier protein synthase II from Streptococcus pneumoniae.
  Acta Crystallogr D Biol Crystallogr, 64, 141-148.
PDB code: 2rjt
18075728 G.Wu, Y.Wu, L.Xiao, X.Li, and C.Lu (2008).
Zero erucic acid trait of rapeseed (Brassica napus L.) results from a deletion of four base pairs in the fatty acid elongase 1 gene.
  Theor Appl Genet, 116, 491-499.  
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
17653358 A.C.Mercer, and M.D.Burkart (2007).
The ubiquitous carrier protein--a window to metabolite biosynthesis.
  Nat Prod Rep, 24, 750-773.  
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
17448991 I.B.Lomakin, Y.Xiong, and T.A.Steitz (2007).
The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together.
  Cell, 129, 319-332.
PDB code: 2pff
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
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.  
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
16513976 S.Jenni, M.Leibundgut, T.Maier, and N.Ban (2006).
Architecture of a fungal fatty acid synthase at 5 A resolution.
  Science, 311, 1263-1267.
PDB code: 2cdh
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
16844787 Y.Tang, C.Y.Kim, I.I.Mathews, D.E.Cane, and C.Khosla (2006).
The 2.7-Angstrom crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase.
  Proc Natl Acad Sci U S A, 103, 11124-11129.
PDB code: 2hg4
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.  
15632283 Z.Zhang, S.Kochhar, and M.G.Grigorov (2005).
Descriptor-based protein remote homology identification.
  Protein Sci, 14, 431-444.  
15507492 B.Chakravarty, Z.Gu, S.S.Chirala, S.J.Wakil, and F.A.Quiocho (2004).
Human fatty acid synthase: structure and substrate selectivity of the thioesterase domain.
  Proc Natl Acad Sci U S A, 101, 15567-15572.
PDB code: 1xkt
15112993 G.L.Tang, Y.Q.Cheng, and B.Shen (2004).
Leinamycin biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase.
  Chem Biol, 11, 33-45.  
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.  
15292254 N.Campobasso, M.Patel, I.E.Wilding, H.Kallender, M.Rosenberg, and M.N.Gwynn (2004).
Staphylococcus aureus 3-hydroxy-3-methylglutaryl-CoA synthase: crystal structure and mechanism.
  J Biol Chem, 279, 44883-44888.
PDB codes: 1tvz 1txt
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.  
  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.  
12618179 P.Leadlay, and A.Baerga-Ortiz (2003).
Mammalian fatty acid synthase: closure on a textbook mechanism?
  Chem Biol, 10, 101-103.  
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.  
12354110 B.J.Blacklock, and J.G.Jaworski (2002).
Studies into factors contributing to substrate specificity of membrane-bound 3-ketoacyl-CoA synthases.
  Eur J Biochem, 269, 4789-4798.  
12193782 H.J.Kwon, W.C.Smith, A.J.Scharon, S.H.Hwang, M.J.Kurth, and B.Shen (2002).
C-O bond formation by polyketide synthases.
  Science, 297, 1327-1330.  
12429097 H.Pan, S.Tsai, E.S.Meadows, L.J.Miercke, A.T.Keatinge-Clay, J.O'Connell, C.Khosla, and R.M.Stroud (2002).
Crystal structure of the priming beta-ketosynthase from the R1128 polyketide biosynthetic pathway.
  Structure, 10, 1559-1568.
PDB code: 1mzj
11684695 X.Lu, S.Lin, C.C.Chang, and T.Y.Chang (2002).
Mutant acyl-coenzyme A:cholesterol acyltransferase 1 devoid of cysteine residues remains catalytically active.
  J Biol Chem, 277, 711-718.  
11325930 G.E.Schujman, K.H.Choi, S.Altabe, C.O.Rock, and Mendoza (2001).
Response of Bacillus subtilis to cerulenin and acquisition of resistance.
  J Bacteriol, 183, 3032-3040.  
11286890 J.G.Olsen, A.Kadziola, P.von Wettstein-Knowles, M.Siggaard-Andersen, and S.Larsen (2001).
Structures of beta-ketoacyl-acyl carrier protein synthase I complexed with fatty acids elucidate its catalytic machinery.
  Structure, 9, 233-243.
PDB codes: 1ek4 1f91
11544358 J.W.Campbell, and J.E.Cronan (2001).
Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery.
  Annu Rev Microbiol, 55, 305-332.  
11162234 L.Du, C.Sánchez, and B.Shen (2001).
Hybrid peptide-polyketide natural products: biosynthesis and prospects toward engineering novel molecules.
  Metab Eng, 3, 78-95.  
11341960 M.Ghanevati, and J.G.Jaworski (2001).
Active-site residues of a plant membrane-bound fatty acid elongase beta-ketoacyl-CoA synthase, FAE1 KCS.
  Biochim Biophys Acta, 1530, 77-85.  
11591436 R.J.Heath, S.W.White, and C.O.Rock (2001).
Lipid biosynthesis as a target for antibacterial agents.
  Prog Lipid Res, 40, 467-497.  
11137815 J.M.Jez, M.B.Austin, J.Ferrer, M.E.Bowman, J.Schröder, and J.P.Noel (2000).
Structural control of polyketide formation in plant-specific polyketide synthases.
  Chem Biol, 7, 919-930.
PDB code: 1ee0
11048953 L.Du, C.Sánchez, M.Chen, D.J.Edwards, and B.Shen (2000).
The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase.
  Chem Biol, 7, 623-642.  
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.