TY - JOUR
T1 - Crystal Structure of Dicamba Monooxygenase
T2 - A Rieske Nonheme Oxygenase that Catalyzes Oxidative Demethylation
AU - Dumitru, Razvan
AU - Jiang, Wen Zhi
AU - Weeks, Donald P.
AU - Wilson, Mark A.
N1 - Funding Information:
We thank Dr. Joseph Barycki (University of Nebraska-Lincoln) for his contributions to the initial stages of this study and assistance with figure preparation, Dr. Todd Holyoak (University of Kansas Medical Center) and Dr. John Lipscomb (University of Minnesota) for helpful discussions, the staff of BioCars 14BM-C for synchrotron beam time, and Mark Behrens for technical assistance. D.P.W. acknowledges funding from Monsanto Co. and the Consortium for Plant Biotechnology Research in support of portions of this work. Use of the Advanced Photon Source was supported by the U.S. Department of Energy under Contract No. DE-AC02-06CH11357. Use of the BioCARS Sector 14 was supported by the National Institutes of Health, National Center for Research Resources, under grant number RR007707.
PY - 2009/9/18
Y1 - 2009/9/18
N2 - 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 Å 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.
AB - 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 Å 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.
KW - Rieske protein
KW - X-ray crystallography
KW - nonheme oxygenase
KW - protein structure
KW - xenobiotic degradation
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U2 - 10.1016/j.jmb.2009.07.021
DO - 10.1016/j.jmb.2009.07.021
M3 - Article
C2 - 19616011
AN - SCOPUS:69049107348
SN - 0022-2836
VL - 392
SP - 498
EP - 510
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 2
ER -