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PDBsum entry 1q7b

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1q7b
Jmol
Contents
Protein chains
243 a.a. *
Ligands
NAP ×4
Metals
_CA ×8
Waters ×502
* Residue conservation analysis
PDB id:
1q7b
Name: Oxidoreductase
Title: The structure of betaketoacyl-[acp] reductase from e. Coli in complex with NADP+
Structure: 3-oxoacyl-[acyl-carrier protein] reductase. Chain: a, b, c, d. Synonym: betaketoacyl-[acp] reductase. 3-ketoacyl-acyl carrier protein reductase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
2.05Å     R-factor:   0.200     R-free:   0.221
Authors: A.C.Price,Y.-M.Zhang,C.O.Rock,S.M.White
Key ref:
A.C.Price et al. (2004). Cofactor-induced conformational rearrangements establish a catalytically competent active site and a proton relay conduit in FabG. Structure, 12, 417-428. PubMed id: 15016358 DOI: 10.1016/j.str.2004.02.008
Date:
17-Aug-03     Release date:   17-Feb-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0AEK2  (FABG_ECOLI) -  3-oxoacyl-[acyl-carrier-protein] reductase FabG
Seq:
Struc:
244 a.a.
243 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   8 terms 
  Biochemical function     oxidoreductase activity     6 terms  

 

 
DOI no: 10.1016/j.str.2004.02.008 Structure 12:417-428 (2004)
PubMed id: 15016358  
 
 
Cofactor-induced conformational rearrangements establish a catalytically competent active site and a proton relay conduit in FabG.
A.C.Price, Y.M.Zhang, C.O.Rock, S.W.White.
 
  ABSTRACT  
 
beta-Ketoacyl-acyl carrier protein reductase (FabG) is a key component in the type II fatty acid synthase system. The structures of Escherichia coli FabG and mutant in binary complexes with NADP(H) reveal that mechanistically important conformational changes accompany cofactor binding. The active site Ser-Tyr-Lys triad is repositioned into a catalytically competent constellation, and a hydrogen bonded network consisting of ribose hydroxyls, the Ser-Tyr-Lys triad, and four water molecules creates a proton wire to replenish the tyrosine proton donated during catalysis. Also, a disordered loop in FabG forms a substructure in the complex that shapes the entrance to the active site. A key observation is that the nicotinamide portion of the cofactor is disordered in the FabG[Y151F].NADP(H) complex, and Tyr151 appears to be necessary for is defective in NADPH binding. Finally, structural changes consistent with the observed negative cooperativity of FabG are described.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Structural Rearrangements Explain the Allosteric Behavior of FabG
In the two panels, the α helices of monomer A are orange, the β strands and coils of monomer A are yellow, the α helices of monomer B are blue, and the β strands and coils of monomer B are green.
(A) A close up of the FabG intermonomer interface at region “c” as defined in Figure 1B. Glu168′ from one monomer forms hydrogen bonds to the amide nitrogens of Leu95 and Met96 on the adjacent monomer, and residues N-terminal to Gly147 on the β5-α5 loop are disordered.
(B) A close up of the same region in the FabG·NADP^+ complex. Note that Glu168′ has shifted its hydrogen bond register to the amide nitrogens of Leu95 and Gly147, and the residues N-terminal to Gly147 on the β5-α5 loop are now ordered. The figure was produced using MOLSCRIPT (Kraulis, 1991) and rendered with RASTER3D (Merritt and Murphy, 1994).
Figure 8.
Figure 8. An Overview of the Interacting Monomers in the FabG·NADP^+ Complex
Glu168′ and its hydrogen bonding interactions, as depicted in Figure 5B, are shown at the interface. Shown in monomer A are the bound cofactor, the active site residues, the ordered β5-α5 loop (purple), and Asn145, which we propose may interact with the incoming pantetheine moiety of the ACP-bound substrate. Shown in monomer B are Arg129′ and Arg172′, which interact with the incoming ACP (Zhang et al., 2003b). The figure was produced using MOLSCRIPT (Kraulis, 1991) and rendered with RASTER3D (Merritt and Murphy, 1994).
 
  The above figures are reprinted by permission from Cell Press: Structure (2004, 12, 417-428) copyright 2004.  
  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
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
20731893 T.Maier, M.Leibundgut, D.Boehringer, and N.Ban (2010).
Structure and function of eukaryotic fatty acid synthases.
  Q Rev Biophys, 43, 373-422.  
19362634 S.C.Tsai, and B.D.Ames (2009).
Structural enzymology of polyketide synthases.
  Methods Enzymol, 459, 17-47.  
17894349 N.R.Zaccai, L.G.Carter, N.S.Berrow, S.Sainsbury, J.E.Nettleship, T.S.Walter, K.Harlos, R.J.Owens, K.S.Wilson, D.I.Stuart, and R.M.Esnouf (2008).
Crystal structure of a 3-oxoacyl-(acylcarrier protein) reductase (BA3989) from Bacillus anthracis at 2.4-A resolution.
  Proteins, 70, 562-567.
PDB code: 2uvd
18772430 T.Maier, M.Leibundgut, and N.Ban (2008).
The crystal structure of a mammalian fatty acid synthase.
  Science, 321, 1315-1322.
PDB codes: 2vz8 2vz9
18205400 T.P.Korman, Y.H.Tan, J.Wong, R.Luo, and S.C.Tsai (2008).
Inhibition kinetics and emodin cocrystal structure of a type II polyketide ketoreductase.
  Biochemistry, 47, 1837-1847.
PDB codes: 2rh4 2rhc 2rhr
18708355 W.Li, J.Ju, S.R.Rajski, H.Osada, and B.Shen (2008).
Characterization of the Tautomycin Biosynthetic Gene Cluster from Streptomyces spiroverticillatus Unveiling New Insights into Dialkylmaleic Anhydride and Polyketide Biosynthesis.
  J Biol Chem, 283, 28607-28617.  
17112527 D.J.Ferguson, S.A.Campbell, F.L.Henriquez, L.Phan, E.Mui, T.A.Richards, S.P.Muench, M.Allary, J.Z.Lu, S.T.Prigge, F.Tomley, M.W.Shirley, D.W.Rice, R.McLeod, and C.W.Roberts (2007).
Enzymes of type II fatty acid synthesis and apicoplast differentiation and division in Eimeria tenella.
  Int J Parasitol, 37, 33-51.  
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
17958702 K.S.Paithankar, C.Feller, E.B.Kuettner, A.Keim, M.Grunow, and N.Sträter (2007).
Cosubstrate-induced dynamics of D-3-hydroxybutyrate dehydrogenase from Pseudomonas putida.
  FEBS J, 274, 5767-5779.
PDB codes: 2q2q 2q2v 2q2w
  17277451 Q.Mao, W.L.Duax, and T.C.Umland (2007).
Crystallization and X-ray diffraction analysis of the beta-ketoacyl-acyl carrier protein reductase FabG from Aquifex aeolicus VF5.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 106-109.  
17431175 S.Jenni, M.Leibundgut, D.Boehringer, C.Frick, B.Mikolásek, and N.Ban (2007).
Structure of fungal fatty acid synthase and implications for iterative substrate shuttling.
  Science, 316, 254-261.
PDB codes: 2uv9 2uva 2uvb 2uvc
17327670 S.P.Muench, S.T.Prigge, R.McLeod, J.B.Rafferty, M.J.Kirisits, C.W.Roberts, E.J.Mui, and D.W.Rice (2007).
Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents.
  Acta Crystallogr D Biol Crystallogr, 63, 328-338.
PDB codes: 2o2s 2o2y 2o50
17898897 S.Smith, and S.C.Tsai (2007).
The type I fatty acid and polyketide synthases: a tale of two megasynthases.
  Nat Prod Rep, 24, 1041-1072.  
16624803 D.J.Miller, Y.M.Zhang, C.O.Rock, and S.W.White (2006).
Structure of RhlG, an essential beta-ketoacyl reductase in the rhamnolipid biosynthetic pathway of Pseudomonas aeruginosa.
  J Biol Chem, 281, 18025-18032.
PDB code: 2b4q
16934037 K.Karmodiya, and N.Surolia (2006).
Analyses of co-operative transitions in Plasmodium falciparum beta-ketoacyl acyl carrier protein reductase upon co-factor and acyl carrier protein binding.
  FEBS J, 273, 4093-4103.  
16648134 Y.M.Zhang, S.W.White, and C.O.Rock (2006).
Inhibiting bacterial fatty acid synthesis.
  J Biol Chem, 281, 17541-17544.  
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.  
15727041 R.J.Wilson (2005).
Parasite plastids: approaching the endgame.
  Biol Rev Camb Philos Soc, 80, 129-153.  
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.  
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
15133034 Y.M.Zhang, and C.O.Rock (2004).
Evaluation of epigallocatechin gallate and related plant polyphenols as inhibitors of the FabG and FabI reductases of bacterial type II fatty-acid synthase.
  J Biol Chem, 279, 30994-31001.  
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.  
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.