Structure and mechanism of the Propionibacterium acnes polyunsaturated fatty acid isomerase.
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.
Department of Plant Biochemistry, University of Göttingen, D-37077 Göttingen, Germany.
Alena
A
Liavonchanka
Ellen
E
Hornung
Ivo
I
Feussner
Markus Georg
MG
Rudolph
D000595:Amino Acid Sequence; D019748:Carbon-Carbon Double Bond Isomerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D003461:Crystallography; D005231:Fatty Acids, Unsaturated / Q000737:chemistry* / Q000378:metabolism; D007536:Isomerism; D008969:Molecular Sequence Data; D011425:Propionibacterium acnes / Q000201:enzymology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D005231:Fatty Acids, Unsaturated; D019748:Carbon-Carbon Double Bond Isomerases; C105113:polyenoic fatty acid isomerase