Acta Crystallographica Section D

Biological Crystallography

Volume 69, Part 12 (December 2013)

research papers

Acta Cryst. (2013). D69, 2340-2352    [ doi:10.1107/S0907444913021859 ]

Structure of the prolyl-acyl carrier protein oxidase involved in the biosynthesis of the cyanotoxin anatoxin-a

K. Moncoq, L. Regad, S. Mann, A. Méjean and O. Ploux

Abstract: Anatoxin-a and homoanatoxin-a are two potent cyano­bacterial neurotoxins biosynthesized from L-proline by a short pathway involving polyketide synthases. Proline is first loaded onto AnaD, an acyl carrier protein, and prolyl-AnaD is then oxidized to 1-pyrroline-5-carboxyl-AnaD by a flavo­protein, AnaB. Three polyketide synthases then transform this imine into anatoxin-a or homoanatoxin-a. AnaB was crystallized in its holo form and its three-dimensional structure was determined by X-ray diffraction at 2.8 Å resolution. AnaB is a homotetramer and its fold is very similar to that of the acyl-CoA dehydrogenases (ACADs). The active-site base of AnaB, Glu244, superimposed very well with that of human isovaleryl-CoA dehydrogenase, confirming previous site-directed mutagenesis experiments and mechanistic proposals. The substrate-binding site of AnaB is small and is likely to be fitted for the pyrrolidine ring of proline. However, in contrast to ACADs, which use an electron-transport protein, AnaB uses molecular oxygen as the electron acceptor, as in acyl-CoA oxidases. Calculation of the solvent-accessible surface area around the FAD in AnaB and in several homologues showed that it is significantly larger in AnaB than in its homologues. A protonated histidine near the FAD in AnaB is likely to participate in oxygen activation. Furthermore, an array of water molecules detected in the AnaB structure suggests a possible path for molecular oxygen towards FAD. This is consistent with AnaB being an oxidase rather than a dehydrogenase. The structure of AnaB is the first to be described for a prolyl-ACP oxidase and it will contribute to defining the structural basis responsible for oxygen reactivity in flavoenzymes.

PDB reference: 4irn

Keywords: anatoxin-a; homoanatoxin-a; acyl-CoA oxidase; acyl-CoA dehydrogenase; flavin; proline.

pdfdisplay filedownload file

Portable Document Format (PDF) file (5207.4 kbytes)
[ doi:10.1107/S0907444913021859/mh5096sup1.pdf ]
Supplementary material


To open or display or play some files, you may need to set your browser up to use the appropriate software. See the full list of file types for an explanation of the different file types and their related mime types and, where available links to sites from where the appropriate software may be obtained.

The download button will force most browsers to prompt for a file name to store the data on your hard disk.

Where possible, images are represented by thumbnails.

 bibliographic record in  format

  Find reference:   Volume   Page   
  Search:     From   to      Advanced search

Copyright © International Union of Crystallography
IUCr Webmaster