Limits...
Identification of a novel Baeyer-Villiger monooxygenase from Acinetobacter radioresistens: close relationship to the Mycobacterium tuberculosis prodrug activator EtaA.

Minerdi D, Zgrablic I, Sadeghi SJ, Gilardi G - Microb Biotechnol (2012)

Bottom Line: Phylogenetic analysis placed the sequence of this novel BVMO in the same clade of the prodrug activator ethionamide monooxygenase (EtaA) and it bears only a distant relation to the other known class I BVMO proteins.In silico analysis of the 3D model of the S13 BVMO generated by homology modelling also supports the similarities with EtaA by binding ethionamide to the active site.In vitro experiments carried out with the purified enzyme confirm that this novel BVMO is indeed capable of typical Baeyer-Villiger reactions as well as oxidation of the prodrug ethionamide.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences and Systems Biology, University of Torino, via Accademia Albertina 13, 10123 Torino, Italy.

Show MeSH

Related in: MedlinePlus

A. Ramachandran plot of the Ar‐BVMO model. The most favoured regions are represented in red, additional allowed regions in dark yellow, generously allowed regions in light yellow.B. Ribbon representation of the 3D model for the Ar‐BVMO based on the crystal structure of cyclohexanone monooxygenase from Rhodococcus sp. (PDB ID = 3GWF). NADPH and FAD are shown in red and yellow respectively.C. Docked ethionamide into the active site of Ar‐BVMO model. FAD is shown in yellow, NADPH in grey, the substrate is in dark blue. The S nucleophilic attack site of the ethionamide is highlighted with a yellow circle and the distance (4 Å) from the C4 of the FAD isoalloxazine ring is indicated by a double arrow. Residues interacting with the substrates are labelled and shown in red.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3815892&req=5

f7: A. Ramachandran plot of the Ar‐BVMO model. The most favoured regions are represented in red, additional allowed regions in dark yellow, generously allowed regions in light yellow.B. Ribbon representation of the 3D model for the Ar‐BVMO based on the crystal structure of cyclohexanone monooxygenase from Rhodococcus sp. (PDB ID = 3GWF). NADPH and FAD are shown in red and yellow respectively.C. Docked ethionamide into the active site of Ar‐BVMO model. FAD is shown in yellow, NADPH in grey, the substrate is in dark blue. The S nucleophilic attack site of the ethionamide is highlighted with a yellow circle and the distance (4 Å) from the C4 of the FAD isoalloxazine ring is indicated by a double arrow. Residues interacting with the substrates are labelled and shown in red.

Mentions: A good stereochemical quality of the model was found by analysis of the geometrical parameters using the Ramachandran plot (Fig. 7A), which shows how the distribution of the ϕ and ψ angles is well comprised in the allowed regions. 86.1% of the residues are in the most favoured regions and 10.2% are in the additional allowed regions, placing the majority (96.3%) of the residues in the most favoured regions. The carbon‐α ribbon presentation of the 3D model of Ar‐BVMO is shown in Fig. 7B.


Identification of a novel Baeyer-Villiger monooxygenase from Acinetobacter radioresistens: close relationship to the Mycobacterium tuberculosis prodrug activator EtaA.

Minerdi D, Zgrablic I, Sadeghi SJ, Gilardi G - Microb Biotechnol (2012)

A. Ramachandran plot of the Ar‐BVMO model. The most favoured regions are represented in red, additional allowed regions in dark yellow, generously allowed regions in light yellow.B. Ribbon representation of the 3D model for the Ar‐BVMO based on the crystal structure of cyclohexanone monooxygenase from Rhodococcus sp. (PDB ID = 3GWF). NADPH and FAD are shown in red and yellow respectively.C. Docked ethionamide into the active site of Ar‐BVMO model. FAD is shown in yellow, NADPH in grey, the substrate is in dark blue. The S nucleophilic attack site of the ethionamide is highlighted with a yellow circle and the distance (4 Å) from the C4 of the FAD isoalloxazine ring is indicated by a double arrow. Residues interacting with the substrates are labelled and shown in red.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815892&req=5

f7: A. Ramachandran plot of the Ar‐BVMO model. The most favoured regions are represented in red, additional allowed regions in dark yellow, generously allowed regions in light yellow.B. Ribbon representation of the 3D model for the Ar‐BVMO based on the crystal structure of cyclohexanone monooxygenase from Rhodococcus sp. (PDB ID = 3GWF). NADPH and FAD are shown in red and yellow respectively.C. Docked ethionamide into the active site of Ar‐BVMO model. FAD is shown in yellow, NADPH in grey, the substrate is in dark blue. The S nucleophilic attack site of the ethionamide is highlighted with a yellow circle and the distance (4 Å) from the C4 of the FAD isoalloxazine ring is indicated by a double arrow. Residues interacting with the substrates are labelled and shown in red.
Mentions: A good stereochemical quality of the model was found by analysis of the geometrical parameters using the Ramachandran plot (Fig. 7A), which shows how the distribution of the ϕ and ψ angles is well comprised in the allowed regions. 86.1% of the residues are in the most favoured regions and 10.2% are in the additional allowed regions, placing the majority (96.3%) of the residues in the most favoured regions. The carbon‐α ribbon presentation of the 3D model of Ar‐BVMO is shown in Fig. 7B.

Bottom Line: Phylogenetic analysis placed the sequence of this novel BVMO in the same clade of the prodrug activator ethionamide monooxygenase (EtaA) and it bears only a distant relation to the other known class I BVMO proteins.In silico analysis of the 3D model of the S13 BVMO generated by homology modelling also supports the similarities with EtaA by binding ethionamide to the active site.In vitro experiments carried out with the purified enzyme confirm that this novel BVMO is indeed capable of typical Baeyer-Villiger reactions as well as oxidation of the prodrug ethionamide.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences and Systems Biology, University of Torino, via Accademia Albertina 13, 10123 Torino, Italy.

Show MeSH
Related in: MedlinePlus