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PDBsum entry 1mzs

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Transferase PDB id
1mzs
Jmol
Contents
Protein chain
317 a.a. *
Ligands
PO4
669
Waters ×177
* Residue conservation analysis
PDB id:
1mzs
Name: Transferase
Title: Crystal structure of beta-ketoacyl-acp synthase iii with bou dichlorobenzyloxy-indole-carboxylic acid inhibitor
Structure: 3-oxoacyl-[acyl-carrier-protein] synthase iii. Chain: a. Synonym: beta-ketoacyl-acp synthase iii, kas iii. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.175     R-free:   0.230
Authors: R.A.Daines,I.Pendrak,K.Sham,G.S.Van Aller,A.K.Konstantinidis J.T.Lonsdale,C.A.Janson,X.Qui,M.Brandt,C.Silverman,M.S.Head
Key ref: R.A.Daines et al. (2003). First X-ray cocrystal structure of a bacterial FabH condensing enzyme and a small molecule inhibitor achieved using rational design and homology modeling. J Med Chem, 46, 5-8. PubMed id: 12502353 DOI: 10.1021/jm025571b
Date:
09-Oct-02     Release date:   13-Nov-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0A6R0  (FABH_ECOLI) -  3-oxoacyl-[acyl-carrier-protein] synthase 3
Seq:
Struc:
317 a.a.
317 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.2.3.1.180  - Beta-ketoacyl-[acyl-carrier-protein] synthase Iii.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacetyl-[acyl-carrier- protein] + CoA + CO2
Acetyl-CoA
+ malonyl-[acyl-carrier-protein]
= acetoacetyl-[acyl-carrier- protein]
+ CoA
+ CO(2)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1021/jm025571b J Med Chem 46:5-8 (2003)
PubMed id: 12502353  
 
 
First X-ray cocrystal structure of a bacterial FabH condensing enzyme and a small molecule inhibitor achieved using rational design and homology modeling.
R.A.Daines, I.Pendrak, K.Sham, G.S.Van Aller, A.K.Konstantinidis, J.T.Lonsdale, C.A.Janson, X.Qiu, M.Brandt, S.S.Khandekar, C.Silverman, M.S.Head.
 
  ABSTRACT  
 
The first cocrystal structure of a bacterial FabH condensing enzyme and a small molecule inhibitor is reported. The inhibitor was obtained by rational modification of a high throughput screening lead with the aid of a S. pneumoniae FabH homology model. This homology model was used to design analogues that would have both high affinity for the enzyme and appropriate aqueous solubility to facilitate cocrystallization studies.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21516317 Y.Pérez-Castillo, M.Froeyen, M.A.Cabrera-Pérez, and A.Nowé (2011).
Molecular dynamics and docking simulations as a proof of high flexibility in E. coli FabH and its relevance for accurate inhibitor modeling.
  J Comput Aided Mol Des, 25, 371-393.  
19191586 P.J.Lee, J.B.Bhonsle, H.W.Gaona, D.P.Huddler, T.N.Heady, M.Kreishman-Deitrick, A.Bhattacharjee, W.F.McCalmont, L.Gerena, M.Lopez-Sanchez, N.E.Roncal, T.H.Hudson, J.D.Johnson, S.T.Prigge, and N.C.Waters (2009).
Targeting the fatty acid biosynthesis enzyme, beta-ketoacyl-acyl carrier protein synthase III (PfKASIII), in the identification of novel antimalarial agents.
  J Med Chem, 52, 952-963.  
18524602 E.Turos, K.D.Revell, P.Ramaraju, D.A.Gergeres, K.Greenhalgh, A.Young, N.Sathyanarayan, S.Dickey, D.Lim, M.M.Alhamadsheh, and K.Reynolds (2008).
Unsymmetric aryl-alkyl disulfide growth inhibitors of methicillin-resistant Staphylococcus aureus and Bacillus anthracis.
  Bioorg Med Chem, 16, 6501-6508.  
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
17114254 H.B.Thomaides, E.J.Davison, L.Burston, H.Johnson, D.R.Brown, A.C.Hunt, J.Errington, and L.Czaplewski (2007).
Essential bacterial functions encoded by gene pairs.
  J Bacteriol, 189, 591-602.  
17456595 J.Wang, S.Kodali, S.H.Lee, A.Galgoci, R.Painter, K.Dorso, F.Racine, M.Motyl, L.Hernandez, E.Tinney, S.L.Colletti, K.Herath, R.Cummings, O.Salazar, I.González, A.Basilio, F.Vicente, O.Genilloud, F.Pelaez, H.Jayasuriya, K.Young, D.F.Cully, and S.B.Singh (2007).
Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic properties.
  Proc Natl Acad Sci U S A, 104, 7612-7616.  
17524982 M.M.Alhamadsheh, F.Musayev, A.A.Komissarov, S.Sachdeva, H.T.Wright, N.Scarsdale, G.Florova, and K.A.Reynolds (2007).
Alkyl-CoA disulfides as inhibitors and mechanistic probes for FabH enzymes.
  Chem Biol, 14, 513-524.
PDB codes: 2eft 2gyo
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.  
16436705 K.Young, H.Jayasuriya, J.G.Ondeyka, K.Herath, C.Zhang, S.Kodali, A.Galgoci, R.Painter, V.Brown-Driver, R.Yamamoto, L.L.Silver, Y.Zheng, J.I.Ventura, J.Sigmund, S.Ha, A.Basilio, F.Vicente, J.R.Tormo, F.Pelaez, P.Youngman, D.Cully, J.F.Barrett, D.Schmatz, S.B.Singh, and J.Wang (2006).
Discovery of FabH/FabF inhibitors from natural products.
  Antimicrob Agents Chemother, 50, 519-526.  
16648134 Y.M.Zhang, S.W.White, and C.O.Rock (2006).
Inhibiting bacterial fatty acid synthesis.
  J Biol Chem, 281, 17541-17544.  
15516341 S.Kodali, A.Galgoci, K.Young, R.Painter, L.L.Silver, K.B.Herath, S.B.Singh, D.Cully, J.F.Barrett, D.Schmatz, and J.Wang (2005).
Determination of selectivity and efficacy of fatty acid synthesis inhibitors.
  J Biol Chem, 280, 1669-1677.  
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.  
15066985 C.Freiberg, N.A.Brunner, G.Schiffer, T.Lampe, J.Pohlmann, M.Brands, M.Raabe, D.Häbich, and K.Ziegelbauer (2004).
Identification and characterization of the first class of potent bacterial acetyl-CoA carboxylase inhibitors with antibacterial activity.
  J Biol Chem, 279, 26066-26073.  
15372084 M.B.Schmid (2004).
Seeing is believing: the impact of structural genomics on antimicrobial drug discovery.
  Nat Rev Microbiol, 2, 739-746.  
15273125 X.He, A.M.Reeve, U.R.Desai, G.E.Kellogg, and K.A.Reynolds (2004).
1,2-dithiole-3-ones as potent inhibitors of the bacterial 3-ketoacyl acyl carrier protein synthase III (FabH).
  Antimicrob Agents Chemother, 48, 3093-3102.  
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.