PDBsum entry 2ba9

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Isomerase PDB id
Protein chain
423 a.a. *
_NA ×2
Waters ×432
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Crystal structure of cla-producing fatty acid isomerase from
Structure: Putative aminooxidase. Chain: a. Synonym: fatty acid isomerase. Engineered: yes
Source: Propionibacterium acnes. Organism_taxid: 1747. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.95Å     R-factor:   0.215     R-free:   0.259
Authors: M.G.Rudoplh,A.Liavonchanka
Key ref:
A.Liavonchanka et al. (2006). Structure and mechanism of the Propionibacterium acnes polyunsaturated fatty acid isomerase. Proc Natl Acad Sci U S A, 103, 2576-2581. PubMed id: 16477020 DOI: 10.1073/pnas.0510144103
14-Oct-05     Release date:   31-Jan-06    
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Protein chain
Pfam   ArchSchema ?
Q6A8X5  (Q6A8X5_PROAC) -  Putative aminooxidase
424 a.a.
423 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   1 term 
  Biochemical function     nucleotide binding     2 terms  


DOI no: 10.1073/pnas.0510144103 Proc Natl Acad Sci U S A 103:2576-2581 (2006)
PubMed id: 16477020  
Structure and mechanism of the Propionibacterium acnes polyunsaturated fatty acid isomerase.
A.Liavonchanka, E.Hornung, I.Feussner, M.G.Rudolph.
Conjugated linoleic acids (CLAs) affect body fat gain, carcinogenesis, insulin resistance, and lipid peroxidation in mammals. Several isomers of CLA exist, of which the (9Z, 11E) and (10E, 12Z) isomers have beneficial effects on human metabolism but are scarce in foods. Bacterial polyunsaturated fatty acid isomerases are promising biotechnological catalysts for CLA production. We describe six crystal structures of the Propionibacterium acnes polyunsaturated fatty acid isomerase PAI in apo- and product-bound forms. The three-domain flavoprotein has previously undescribed folds outside the FAD-binding site. Conformational changes in a hydrophobic channel toward the active site reveal a unique gating mechanism for substrate specificity. The geometry of the substrate-binding site explains the length preferences for C18 fatty acids. A catalytic mechanism for double-bond isomerization is formulated that may be altered to change substrate specificity for syntheses of rare CLAs from easily accessible precursors.
  Selected figure(s)  
Figure 1.
Fig. 1. The PAI reaction and structure. (a) Reaction catalyzed by PAI. (b) [A]-weighted mF[o] – DF[c] omit electron density maps contoured at 2 of FAD and a side-on view of the isoalloxazine ring (Inset). (c) Architecture of PAI with the FAD-binding domain colored in magenta, domain 2 in red, and domain 3 in blue. FAD and PEG 400 are shown as stick models in this stereo figure. (d) PAI structural analogs: polyaminooxidase (PDB ID code 1RSG) (Left), UDP-galactopyranose mutase (1I8T) (Center), and guanine nucleotide dissociation inhibitor (1GND) (Right). The domains are colored as for PAI but in lighter hue.
Figure 3.
Fig. 3. Substrate entry channel and gating mechanism in PAI. (a) The surface potential of PAI shows an electropositive area localized at the entrance of the channel that is created by Lys-85, Arg-87, Lys-102, and Lys-195. The PEG 400 molecule marks the entry of the channel. (b) The molecular surface (blue) of part of the PEG 400 molecule bound to PAI in the absence of substrate/product shows the 30-Å path from the surface to the active site FAD (drawn as sticks). (c) Conformational changes in active site associated with PEG 400 binding reveal the gating mechanism. PEG 400, Phe-193, and Arg-88 are in the open conformation when PEG 400 is bound (blue) compared with the apoenzyme (gray). Arg-88 displays two conformations in the open form of PAI, both of which point away from the entering substrate.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21360616 J.Loch, A.Polit, A.Górecki, P.Bonarek, K.Kurpiewska, M.Dziedzicka-Wasylewska, and K.Lewiński (2011).
Two modes of fatty acid binding to bovine β-lactoglobulin-crystallographic and spectroscopic studies.
  J Mol Recognit, 24, 341-349.
PDB codes: 3npo 3nq3 3nq9
21307591 S.Kishino, J.Ogawa, K.Yokozeki, and S.Shimizu (2011).
Linoleic acid isomerase in Lactobacillus plantarum AKU1009a proved to be a multi-component enzyme system requiring oxidoreduction cofactors.
  Biosci Biotechnol Biochem, 75, 318-322.  
20145247 A.Volkov, A.Liavonchanka, O.Kamneva, T.Fiedler, C.Goebel, B.Kreikemeyer, and I.Feussner (2010).
Myosin cross-reactive antigen of Streptococcus pyogenes M49 encodes a fatty acid double bond hydratase that plays a role in oleic acid detoxification and bacterial virulence.
  J Biol Chem, 285, 10353-10361.  
20825518 M.Macouzet, B.H.Lee, and N.Robert (2010).
Genetic and structural comparison of linoleate isomerases from selected food-grade bacteria.
  J Appl Microbiol, 109, 2128-2134.  
19164287 A.Liavonchanka, M.G.Rudolph, K.Tittmann, M.Hamberg, and I.Feussner (2009).
On the mechanism of a polyunsaturated fatty acid double bond isomerase from Propionibacterium acnes.
  J Biol Chem, 284, 8005-8012.  
19118369 F.M.McIntosh, K.J.Shingfield, E.Devillard, W.R.Russell, and R.J.Wallace (2009).
Mechanism of conjugated linoleic acid and vaccenic acid formation in human faecal suspensions and pure cultures of intestinal bacteria.
  Microbiology, 155, 285-294.  
18655062 A.Liavonchanka, and I.Feussner (2008).
Biochemistry of PUFA double bond isomerases producing conjugated linoleic acid.
  Chembiochem, 9, 1867-1872.  
17897229 D.Paillard, N.McKain, M.T.Rincon, K.J.Shingfield, D.I.Givens, and R.J.Wallace (2007).
Quantification of ruminal Clostridium proteoclasticum by real-time PCR using a molecular beacon approach.
  J Appl Microbiol, 103, 1251-1261.  
17660413 E.Rosberg-Cody, M.C.Johnson, G.F.Fitzgerald, P.R.Ross, and C.Stanton (2007).
Heterologous expression of linoleic acid isomerase from Propionibacterium acnes and anti-proliferative activity of recombinant trans-10, cis-12 conjugated linoleic acid.
  Microbiology, 153, 2483-2490.  
18057448 M.D.Deng, A.D.Grund, K.J.Schneider, K.M.Langley, S.L.Wassink, S.S.Peng, and R.A.Rosson (2007).
Linoleic acid isomerase from Propionibacterium acnes: purification, characterization, molecular cloning, and heterologous expression.
  Appl Biochem Biotechnol, 143, 199-211.  
17070680 L.De Colibus, and A.Mattevi (2006).
New frontiers in structural flavoenzymology.
  Curr Opin Struct Biol, 16, 722-728.  
17124494 M.Kato, R.M.Wynn, J.L.Chuang, C.A.Brautigam, M.Custorio, and D.T.Chuang (2006).
A synchronized substrate-gating mechanism revealed by cubic-core structure of the bovine branched-chain alpha-ketoacid dehydrogenase complex.
  EMBO J, 25, 5983-5994.
PDB codes: 2ihw 2ii3 2ii4 2ii5
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.