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PDBsum entry 1kas

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protein links
Acyltransferase PDB id
1kas
Jmol PyMol
Contents
Protein chain
411 a.a. *
Waters ×31
* Residue conservation analysis
PDB id:
1kas
Name: Acyltransferase
Title: Beta-ketoacyl-acp synthase ii from escherichia coli
Structure: Beta-ketoacyl acp synthase ii. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
2.40Å     R-factor:   0.242     R-free:   0.279
Authors: W.Huang,J.Jia,P.Edwards,K.Dehesh,G.Schneider,Y.Lindqvist
Key ref:
W.Huang et al. (1998). Crystal structure of beta-ketoacyl-acyl carrier protein synthase II from E.coli reveals the molecular architecture of condensing enzymes. EMBO J, 17, 1183-1191. PubMed id: 9482715 DOI: 10.1093/emboj/17.5.1183
Date:
22-Dec-97     Release date:   02-Mar-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0AAI5  (FABF_ECOLI) -  3-oxoacyl-[acyl-carrier-protein] synthase 2
Seq:
Struc:
413 a.a.
411 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.3.1.179  - Beta-ketoacyl-[acyl-carrier-protein] synthase Ii.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (Z)-hexadec-11-enoyl-[acyl-carrier-protein] + malonyl-[acyl-carrier- protein] = (Z)-3-oxooctadec-13-enoyl-[acyl-carrier-protein] + CO2 + [acyl-carrier-protein]
(Z)-hexadec-11-enoyl-[acyl-carrier-protein]
+ malonyl-[acyl-carrier- protein]
= (Z)-3-oxooctadec-13-enoyl-[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     cytosol   1 term 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     7 terms  

 

 
    Added reference    
 
 
DOI no: 10.1093/emboj/17.5.1183 EMBO J 17:1183-1191 (1998)
PubMed id: 9482715  
 
 
Crystal structure of beta-ketoacyl-acyl carrier protein synthase II from E.coli reveals the molecular architecture of condensing enzymes.
W.Huang, J.Jia, P.Edwards, K.Dehesh, G.Schneider, Y.Lindqvist.
 
  ABSTRACT  
 
In the biosynthesis of fatty acids, the beta-ketoacyl-acyl carrier protein (ACP) synthases catalyze chain elongation by the addition of two-carbon units derived from malonyl-ACP to an acyl group bound to either ACP or CoA. The crystal structure of beta-ketoacyl synthase II from Escherichia coli has been determined with the multiple isomorphous replacement method and refined at 2.4 A resolution. The subunit consists of two mixed five-stranded beta-sheets surrounded by alpha-helices. The two sheets are packed against each other in such a way that the fold can be described as consisting of five layers, alpha-beta-alpha-beta-alpha. The enzyme is a homodimer, and the subunits are related by a crystallographic 2-fold axis. The two active sites are located near the dimer interface but are approximately 25 A apart. The proposed nucleophile in the reaction, Cys163, is located at the bottom of a mainly hydrophobic pocket which is also lined with several conserved polar residues. In spite of very low overall sequence homology, the structure of beta-ketoacyl synthase is similar to that of thiolase, an enzyme involved in the beta-oxidation pathway, indicating that both enzymes might have a common ancestor.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Scheme of the chemical steps occuring in the fatty acid elongation reaction catalyzed by -keto acyl synthase.
Figure 4.
Figure 4 Stereo view of the dimer of KAS II, the active site cysteine is shown as a space-filling model (black/yellow and black/green spheres, respectively). The figure was generated with the programs Molscript (Kraulis, 1991) and Raster3D (Merrit and Murphy, 1994).
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1998, 17, 1183-1191) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21113689 O.K.Teh, and U.S.Ramli (2011).
Characterization of a KCS-like KASII from Jessenia bataua that elongates saturated and monounsaturated stearic acids in Arabidopsis thaliana.
  Mol Biotechnol, 48, 97.  
19837798 D.C.Pöther, M.Liebeke, F.Hochgräfe, H.Antelmann, D.Becher, M.Lalk, U.Lindequist, I.Borovok, G.Cohen, Y.Aharonowitz, and M.Hecker (2009).
Diamide triggers mainly S Thiolations in the cytoplasmic proteomes of Bacillus subtilis and Staphylococcus aureus.
  J Bacteriol, 191, 7520-7530.  
19460825 E.M.Vanderlinde, A.Muszynski, J.J.Harrison, S.F.Koval, D.L.Foreman, H.Ceri, E.L.Kannenberg, R.W.Carlson, and C.K.Yost (2009).
Rhizobium leguminosarum biovar viciae 3841, deficient in 27-hydroxyoctacosanoate-modified lipopolysaccharide, is impaired in desiccation tolerance, biofilm formation and motility.
  Microbiology, 155, 3055-3069.  
  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.  
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
17268612 C.Hertweck, A.Luzhetskyy, Y.Rebets, and A.Bechthold (2007).
Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork.
  Nat Prod Rep, 24, 162-190.  
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
  17697396 J.Z.Lu, S.P.Muench, M.Allary, S.Campbell, C.W.Roberts, E.Mui, R.L.McLeod, D.W.Rice, and S.T.Prigge (2007).
Type I and type II fatty acid biosynthesis in Eimeria tenella: enoyl reductase activity and structure.
  Parasitology, 134, 1949-1962.
PDB code: 2ptg
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.  
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
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.  
15286722 A.T.Keatinge-Clay, D.A.Maltby, K.F.Medzihradszky, C.Khosla, and R.M.Stroud (2004).
An antibiotic factory caught in action.
  Nat Struct Mol Biol, 11, 888-893.
PDB code: 1tqy
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.  
15371447 M.S.Kimber, F.Martin, Y.Lu, S.Houston, M.Vedadi, A.Dharamsi, K.M.Fiebig, M.Schmid, and C.O.Rock (2004).
The structure of (3R)-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Pseudomonas aeruginosa.
  J Biol Chem, 279, 52593-52602.
PDB code: 1u1z
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
  15043388 R.J.Heath, and C.O.Rock (2004).
Fatty acid biosynthesis as a target for novel antibacterials.
  Curr Opin Investig Drugs, 5, 146-153.  
15554959 R.Veyron-Churlet, O.Guerrini, L.Mourey, M.Daffé, and D.Zerbib (2004).
Protein-protein interactions within the Fatty Acid Synthase-II system of Mycobacterium tuberculosis are essential for mycobacterial viability.
  Mol Microbiol, 54, 1161-1172.  
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.  
12897013 H.Wang, and J.E.Cronan (2003).
Haemophilus influenzae Rd lacks a stringently conserved fatty acid biosynthetic enzyme and thermal control of membrane lipid composition.
  J Bacteriol, 185, 4930-4937.  
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.  
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.  
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
11325930 G.E.Schujman, K.H.Choi, S.Altabe, C.O.Rock, and D.de 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.  
11451671 P.Caffrey, S.Lynch, E.Flood, S.Finnan, and M.Oliynyk (2001).
Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of polyketide synthase and late genes.
  Chem Biol, 8, 713-723.  
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.  
10673437 C.Davies, R.J.Heath, S.W.White, and C.O.Rock (2000).
The 1.8 A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from escherichia coli.
  Structure, 8, 185-195.
PDB code: 1ebl
10873858 D.Val, G.Banu, K.Seshadri, Y.Lindqvist, and K.Dehesh (2000).
Re-engineering ketoacyl synthase specificity.
  Structure, 8, 565-566.  
10662695 I.Molnár, T.Schupp, M.Ono, R.Zirkle, M.Milnamow, B.Nowak-Thompson, N.Engel, C.Toupet, A.Stratmann, D.D.Cyr, J.Gorlach, J.M.Mayo, A.Hu, S.Goff, J.Schmid, and J.M.Ligon (2000).
The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90.
  Chem Biol, 7, 97.  
10684659 J.Dreier, and C.Khosla (2000).
Mechanistic analysis of a type II polyketide synthase. Role of conserved residues in the beta-ketoacyl synthase-chain length factor heterodimer.
  Biochemistry, 39, 2088-2095.  
11094342 J.F.Aparicio, R.Fouces, M.V.Mendes, N.Olivera, and J.F.Martín (2000).
A complex multienzyme system encoded by five polyketide synthase genes is involved in the biosynthesis of the 26-membered polyene macrolide pimaricin in Streptomyces natalensis.
  Chem Biol, 7, 895-905.  
10653632 J.M.Jez, J.L.Ferrer, M.E.Bowman, R.A.Dixon, and J.P.Noel (2000).
Dissection of malonyl-coenzyme A decarboxylation from polyketide formation in the reaction mechanism of a plant polyketide synthase.
  Biochemistry, 39, 890-902.
PDB codes: 1d6f 1d6h 1d6i
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.  
10762267 M.He, M.Varoglu, and D.H.Sherman (2000).
Structural modeling and site-directed mutagenesis of the actinorhodin beta-ketoacyl-acyl carrier protein synthase.
  J Bacteriol, 182, 2619-2623.  
10966480 R.N.Perham (2000).
Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions.
  Annu Rev Biochem, 69, 961.  
10747780 Y.Jia, T.J.Kappock, T.Frick, A.J.Sinskey, and J.Stubbe (2000).
Lipases provide a new mechanistic model for polyhydroxybutyrate (PHB) synthases: characterization of the functional residues in Chromatium vinosum PHB synthase.
  Biochemistry, 39, 3927-3936.  
10872449 C.Khosla, R.S.Gokhale, J.R.Jacobsen, and D.E.Cane (1999).
Tolerance and specificity of polyketide synthases.
  Annu Rev Biochem, 68, 219-253.  
  10211824 M.G.Rudolph, A.Wittinghofer, and I.R.Vetter (1999).
Nucleotide binding to the G12V-mutant of Cdc42 investigated by X-ray diffraction and fluorescence spectroscopy: two different nucleotide states in one crystal.
  Protein Sci, 8, 778-787.
PDB code: 1a4r
10037680 M.Moche, G.Schneider, P.Edwards, K.Dehesh, and Y.Lindqvist (1999).
Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase.
  J Biol Chem, 274, 6031-6034.
PDB code: 1b3n
10593943 X.Qiu, C.A.Janson, A.K.Konstantinidis, S.Nwagwu, C.Silverman, W.W.Smith, S.Khandekar, J.Lonsdale, and S.S.Abdel-Meguid (1999).
Crystal structure of beta-ketoacyl-acyl carrier protein synthase III. A key condensing enzyme in bacterial fatty acid biosynthesis.
  J Biol Chem, 274, 36465-36471.
PDB code: 1hn9
10545327 Y.Modis, and R.K.Wierenga (1999).
A biosynthetic thiolase in complex with a reaction intermediate: the crystal structure provides new insights into the catalytic mechanism.
  Structure, 7, 1279-1290.
PDB code: 1qfl
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.

 

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