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Structure of the prolyl-acyl carrier protein oxidase involved in the biosynthesis of the cyanotoxin anatoxin-a
- Source :
- Acta Crystallographica Section D Biological Crystallography. 69:2340-2352
- Publication Year :
- 2013
- Publisher :
- International Union of Crystallography (IUCr), 2013.
-
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.
- Subjects :
- Models, Molecular
Bacterial Toxins
Molecular Sequence Data
Flavoprotein
Dehydrogenase
Flavin group
Crystallography, X-Ray
Cyanobacteria
ACADS
Acyl-CoA Dehydrogenases
Structural Biology
Oxidoreductase
Acyl Carrier Protein
Animals
Humans
Amino Acid Sequence
chemistry.chemical_classification
Oxidase test
Cyanobacteria Toxins
biology
General Medicine
Bridged Bicyclo Compounds, Heterocyclic
Acyl carrier protein
chemistry
Biochemistry
biology.protein
Oxidoreductases
Sequence Alignment
Tropanes
Homotetramer
Subjects
Details
- ISSN :
- 09074449
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Acta Crystallographica Section D Biological Crystallography
- Accession number :
- edsair.doi.dedup.....e24a21d24a4b2406ececd8bed568d25d
- Full Text :
- https://doi.org/10.1107/s0907444913021859