The acyl-CoA reductase, LuxC, isolated from Photobacterium phosphoreum , has been found to have a low sequence identity to aldehyde dehydrogenases, particularly in the more conserved regions (i.e. motifs) containing the active site residues. Mutational studies on residues involved in cofactor binding and in catalysis conserved in both the LuxC enzyme and in Vibrio harveyi aldehyde dehydrogenase have shown that these residues may play similar roles as the effects of mutation on the kinetic parameters of the two enzymes were found to be very similar. Moreover, preliminary X-ray structural characterization of LuxC shows that its overall structure and fold is very similar to that of the V. harveyi aldehyde dehydrogenase. Both enzymes are able to bind their NAD(P)(H) cofactors in much the same way and the beta-sheet extension that is seen upon dimer formation in the V. harveyi enzyme is also seen in the P. phosphoreum enzyme. Given these results, and the fact that PpLuxC and Vh-ALDH have polypeptides of very similar size that can catalyze similar reactions, albeit in opposite directions, we are proposing that the acyl-CoA reductase of P. phosphoreum is part of the aldehyde dehydrogenase extended family, making it the first member of this family to preferentially catalyze the reduction of fatty acids to aldehydes rather than the oxidation of fatty aldehydes to acids. Finally, through the study of a critical glutamate residue of V. harveyi aldehyde dehydrogenase, we have provided direct evidence that this residue may be the critical determinant in deciding whether aldehyde oxidation or acid reduction is catalyzed preferentially.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.81441 |
| Date | January 2004 |
| Creators | Skouris, Nicolas |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002166533, proquestno: AAIMR06456, Theses scanned by UMI/ProQuest. |
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