title: Crystal structure of dicamba monooxygenase: a Rieske nonheme oxygenase that catalyzes oxidative demethylation.
abstract: Dicamba (3,6-dichloro-2-methoxybenzoic acid) is a widely used herbicide that is efficiently degraded by soil microbes. These microbes use a novel Rieske nonheme oxygenase, dicamba monooxygenase (DMO), to catalyze the oxidative demethylation of dicamba to 3,6-dichlorosalicylic acid (DCSA) and formaldehyde. We have determined the crystal structures of DMO in the free state, bound to its substrate dicamba, and bound to the product DCSA at 2.10-1.75 A resolution. The structures show that the DMO active site uses a combination of extensive hydrogen bonding and steric interactions to correctly orient chlorinated, ortho-substituted benzoic-acid-like substrates for catalysis. Unlike other Rieske aromatic oxygenases, DMO oxygenates the exocyclic methyl group, rather than the aromatic ring, of its substrate. This first crystal structure of a Rieske demethylase shows that the Rieske oxygenase structural scaffold can be co-opted to perform varied types of reactions on xenobiotic substrates.
authors.affiliation: Department of Biochemistry, The University of Nebraska-Lincoln, Lincoln, NE 68588-0664, USA.
authors.forename: Razvan
authors.initials: R
authors.lastname: Dumitru
authors.forename: Wen Zhi
authors.initials: WZ
authors.lastname: Jiang
authors.forename: Donald P
authors.initials: DP
authors.lastname: Weeks
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wilson
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D002723:Chlorobenzoates; D018360:Crystallography, X-Ray; D003996:Dicamba / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012459:Salicylates / Q000378:metabolism; D020615:Stenotrophomonas maltophilia / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D002723:Chlorobenzoates; D012459:Salicylates; C487853:3,6-dichlorosalicylic acid; D006899:Mixed Function Oxygenases; D003996:Dicamba