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protein ligands Protein-protein interface(s) links
Transferase PDB id
2qnz
Jmol
Contents
Protein chains
330 a.a. *
Ligands
DFD ×2
BME ×2
Waters ×367
* Residue conservation analysis
PDB id:
2qnz
Name: Transferase
Title: Crystal structure of the complex between the mycobacterium beta-ketoacyl-acyl carrier protein synthase iii (fabh) and ss-(2-hydroxyethyl)-o-decyl ester carbono(dithioperoxoic) acid
Structure: 3-oxoacyl-[acyl-carrier-protein] synthase 3. Chain: a, b. Synonym: 3-oxoacyl- [acyl-carrier-protein] synthase iii, beta-ketoacyl-acp synthase iii, kas iii, mtfabh. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: fabh. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.170     R-free:   0.222
Authors: S.Sachdeva,F.Musayev,M.Alhamadsheh,J.N.Scarsdale,H.T.Wright, K.A.Reynolds
Key ref: S.Sachdeva et al. (2008). Separate entrance and exit portals for ligand traffic in Mycobacterium tuberculosis FabH. Chem Biol, 15, 402-412. PubMed id: 18420147 DOI: 10.1016/j.chembiol.2008.03.007
Date:
19-Jul-07     Release date:   06-May-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A574  (FABH_MYCTU) -  3-oxoacyl-[acyl-carrier-protein] synthase 3
Seq:
Struc: 		335 a.a.
330 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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)
Bound ligand (Het Group name = BME)
matches with 40.00% similarity
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     9 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.chembiol.2008.03.007 Chem Biol 15:402-412 (2008)
PubMed id: 18420147  
 
 
Separate entrance and exit portals for ligand traffic in Mycobacterium tuberculosis FabH.
S.Sachdeva, F.N.Musayev, M.M.Alhamadsheh, J.N.Scarsdale, H.T.Wright, K.A.Reynolds.
 
  ABSTRACT  
 
Mycobacterium tuberculosis FabH initiates type II fatty acid synthase-catalyzed formation of the long chain (C(16)-C(22)) acyl-coenzyme A (CoA) precursors of mycolic acids, which are major constituents of the bacterial cell envelope. Crystal structures of M. tuberculosis FabH (mtFabH) show the substrate binding site to be a buried, extended L-shaped channel with only a single solvent access portal. Entrance of an acyl-CoA substrate through the solvent portal would require energetically unfavorable reptational threading of the substrate to its reactive position. Using a class of FabH inhibitors, we have tested an alternative hypothesis that FabH exists in an "open" form during substrate binding and product release, and a "closed" form in which catalysis and intermediate steps occur. This hypothesis is supported by mass spectrometric analysis of the product profile and crystal structures of complexes of mtFabH with these inhibitors.
 

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.  
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.  
19694421 A.K.Bera, V.Atanasova, H.Robinson, E.Eisenstein, J.P.Coleman, E.C.Pesci, and J.F.Parsons (2009).
Structure of PqsD, a Pseudomonas quinolone signal biosynthetic enzyme, in complex with anthranilate.
  Biochemistry, 48, 8644-8655.
PDB codes: 3h76 3h77 3h78
19847268 J.M.Crawford, T.P.Korman, J.W.Labonte, A.L.Vagstad, E.A.Hill, O.Kamari-Bidkorpeh, S.C.Tsai, and C.A.Townsend (2009).
Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization.
  Nature, 461, 1139-1143.
PDB codes: 3hrq 3hrr
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.  
19440303 Q.Al-Balas, N.G.Anthony, B.Al-Jaidi, A.Alnimr, G.Abbott, A.K.Brown, R.C.Taylor, G.S.Besra, T.D.McHugh, S.H.Gillespie, B.F.Johnston, S.P.Mackay, and G.D.Coxon (2009).
Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H(37)R(v) and the beta-Ketoacyl-ACP Synthase mtFabH.
  PLoS ONE, 4, e5617.  
19604470 S.Swanson, K.Gokulan, and J.C.Sacchettini (2009).
KasA, another brick in the mycobacterial cell wall.
  Structure, 17, 914-915.  
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.  
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.