PDBsum entry 1uzn

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Jmol PyMol
Protein chains
239 a.a. *
226 a.a. *
_CS ×4
Waters ×271
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Maba from mycobacterium tuberculosis
Structure: 3-oxoacyl-[acyl-carrier protein] reductase. Chain: a, b. Synonym: reductase, 3-ketoacyl-acyl carrier protein reducta engineered: yes. Mutation: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PDB file)
1.91Å     R-factor:   0.187     R-free:   0.227
Authors: M.Cohen-Gonsaud,S.Ducasse,A.Quemard,G.Labesse
Key ref:
M.Cohen-Gonsaud et al. (2002). Crystal structure of MabA from Mycobacterium tuberculosis, a reductase involved in long-chain fatty acid biosynthesis. J Mol Biol, 320, 249-261. PubMed id: 12079383 DOI: 10.1016/S0022-2836(02)00463-1
14-Mar-04     Release date:   23-Mar-05    
Go to PROCHECK summary

Protein chain
P9WGT3  (FABG_MYCTU) -  3-oxoacyl-[acyl-carrier-protein] reductase FabG1
247 a.a.
239 a.a.*
Protein chain
P9WGT3  (FABG_MYCTU) -  3-oxoacyl-[acyl-carrier-protein] reductase FabG1
247 a.a.
226 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - 3-oxoacyl-[acyl-carrier-protein] reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP+ = 3-oxoacyl-[acyl- carrier-protein] + NADPH
Bound ligand (Het Group name = NAP)
matches with 62.00% similarity
= 3-oxoacyl-[acyl- carrier-protein]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     plasma membrane   1 term 
  Biological process     mycolic acid biosynthetic process   6 terms 
  Biochemical function     protein binding     6 terms  


DOI no: 10.1016/S0022-2836(02)00463-1 J Mol Biol 320:249-261 (2002)
PubMed id: 12079383  
Crystal structure of MabA from Mycobacterium tuberculosis, a reductase involved in long-chain fatty acid biosynthesis.
M.Cohen-Gonsaud, S.Ducasse, F.Hoh, D.Zerbib, G.Labesse, A.Quemard.
The fatty acid elongation system FAS-II is involved in the biosynthesis of mycolic acids, which are major and specific long-chain fatty acids of the cell envelope of Mycobacterium tuberculosis and other mycobacteria, including Mycobacterium smegmatis. The protein MabA, also named FabG1, has been shown recently to be part of FAS-II and to catalyse the NADPH-specific reduction of long chain beta-ketoacyl derivatives. This activity corresponds to the second step of an FAS-II elongation round. FAS-II is inhibited by the antituberculous drug isoniazid through the inhibition of the 2-trans-enoyl-acyl carrier protein reductase InhA. Thus, the other enzymes making up this enzymatic complex represent potential targets for designing new antituberculous drugs. The crystal structure of the apo-form MabA was solved to 2.03 A resolution by molecular replacement. MabA is tetrameric and shares the conserved fold of the short-chain dehydrogenases/reductases (SDRs). However, it exhibits some significant local rearrangements of the active-site loops in the absence of a cofactor, particularly the beta5-alpha5 region carrying the unique tryptophan residue, in agreement with previous fluorescence spectroscopy data. A similar conformation has been observed in the beta-ketoacyl reductase from Escherichia coli and the distantly related dehydratase. The distinctive enzymatic and structural properties of MabA are discussed in view of its crystal structure and that of related enzymes.
  Selected figure(s)  
Figure 6.
Figure 6. Global fold and topology of the crystal structure of MabA. The secondary elements are numbered in order to highlight the similarity with the classical Rossmann fold. The figure was produced using Swiss-PdbViewer and POV-Ray™.
Figure 10.
Figure 10. Structure comparison of the active-site region of holo-KARbn and MabA. MabA is represented in green, holo-KARbn (PDB1EDO) in red, the superposition was made on the whole common core (described in the text). In the absence of cofactor, the superposition shows an important rearrangement of β5, and the rotation of the catalytic tyrosineresidue (Tyr153 in MabA and Tyr167 in KARbn). The Figure was produced using the program InsightII (MSI, USA).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 320, 249-261) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21081168 D.Dutta, S.Bhattacharyya, S.Mukherjee, B.Saha, and A.K.Das (2011).
Crystal structure of FabG4 from Mycobacterium tuberculosis reveals the importance of C-terminal residues in ketoreductase activity.
  J Struct Biol, 174, 147-155.
PDB code: 3m1l
21204864 G.Gago, L.Diacovich, A.Arabolaza, S.C.Tsai, and H.Gramajo (2011).
Fatty acid biosynthesis in actinomycetes.
  FEMS Microbiol Rev, 35, 475-497.  
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.  
19444866 D.Wu, X.D.Wu, X.F.You, X.F.Ma, and W.X.Tian (2010).
Inhibitory effects on bacterial growth and beta-ketoacyl-ACP reductase by different species of maple leaf extracts and tannic acid.
  Phytother Res, 24, S35-S41.  
20340135 R.Huether, Q.Mao, W.L.Duax, and T.C.Umland (2010).
The short-chain oxidoreductase Q9HYA2 from Pseudomonas aeruginosa PAO1 contains an atypical catalytic center.
  Protein Sci, 19, 1097-1103.
PDB codes: 3lf1 3lf2
19074144 R.Veyron-Churlet, V.Molle, R.C.Taylor, A.K.Brown, G.S.Besra, I.Zanella-Cléon, K.Fütterer, and L.Kremer (2009).
The Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III activity is inhibited by phosphorylation on a single threonine residue.
  J Biol Chem, 284, 6414-6424.  
20477209 H.Tomioka, Y.Tatano, K.Yasumoto, and T.Shimizu (2008).
Recent advances in antituberculous drug development and novel drug targets.
  Expert Rev Respir Med, 2, 455-471.  
19099550 K.Raman, Y.Kalidas, and N.Chandra (2008).
targetTB: A target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis.
  BMC Syst Biol, 2, 109.  
17642518 G.Poncet-Montange, S.Ducasse-Cabanot, A.Quemard, G.Labesse, and M.Cohen-Gonsaud (2007).
Lack of dynamics in the MabA active site kills the enzyme activity: practical consequences for drug-design studies.
  Acta Crystallogr D Biol Crystallogr, 63, 923-925.
PDB code: 2ntn
16085817 C.T.Nomura, K.Taguchi, Z.Gan, K.Kuwabara, T.Tanaka, K.Takase, and Y.Doi (2005).
Expression of 3-ketoacyl-acyl carrier protein reductase (fabG) genes enhances production of polyhydroxyalkanoate copolymer from glucose in recombinant Escherichia coli JM109.
  Appl Environ Microbiol, 71, 4297-4306.  
15970585 E.K.Bomati, M.B.Austin, M.E.Bowman, R.A.Dixon, and J.P.Noel (2005).
Structural elucidation of chalcone reductase and implications for deoxychalcone biosynthesis.
  J Biol Chem, 280, 30496-30503.
PDB code: 1zgd
15653820 K.Takayama, C.Wang, and G.S.Besra (2005).
Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis.
  Clin Microbiol Rev, 18, 81.  
15977159 M.Cohen-Gonsaud, S.Ducasse-Cabanot, A.Quemard, and G.Labesse (2005).
Ligand-induced fit in mycobacterial MabA: the sequence-specific C-terminus locks the conformational change.
  Proteins, 60, 392-400.  
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.  
15016358 A.C.Price, Y.M.Zhang, C.O.Rock, and S.W.White (2004).
Cofactor-induced conformational rearrangements establish a catalytically competent active site and a proton relay conduit in FabG.
  Structure, 12, 417-428.
PDB codes: 1q7b 1q7c
15109786 L.G.Dover, A.M.Cerdeño-Tárraga, M.J.Pallen, J.Parkhill, and G.S.Besra (2004).
Comparative cell wall core biosynthesis in the mycolated pathogens, Mycobacterium tuberculosis and Corynebacterium diphtheriae.
  FEMS Microbiol Rev, 28, 225-250.  
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.  
14693546 S.Ducasse-Cabanot, M.Cohen-Gonsaud, H.Marrakchi, M.Nguyen, D.Zerbib, J.Bernadou, M.Daffé, G.Labesse, and A.Quémard (2004).
In vitro inhibition of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein reductase MabA by isoniazid.
  Antimicrob Agents Chemother, 48, 242-249.  
15544323 T.P.Korman, J.A.Hill, T.N.Vu, and S.C.Tsai (2004).
Structural analysis of actinorhodin polyketide ketoreductase: cofactor binding and substrate specificity.
  Biochemistry, 43, 14529-14538.
PDB codes: 1x7g 1x7h 1xr3
15726819 Y.M.Zhang, Y.J.Lu, and C.O.Rock (2004).
The reductase steps of the type II fatty acid synthase as antimicrobial targets.
  Lipids, 39, 1055-1060.  
14675542 C.V.Smith, and J.C.Sacchettini (2003).
Mycobacterium tuberculosis: a model system for structural genomics.
  Curr Opin Struct Biol, 13, 658-664.  
12915092 M.Bellinzoni, and G.Riccardi (2003).
Techniques and applications: The heterologous expression of Mycobacterium tuberculosis genes is an uphill road.
  Trends Microbiol, 11, 351-358.  
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.