Structure and function of the two-component flavin-dependent methanesulfinate monooxygenase within bacterial sulfur assimilation

Jess Soule; Andrew D Gnann; Reyaz Gonzalez; Mackenzie J Parker; Kylie C McKenna; Son V Nguyen; Ngan T Phan; Denyce K Wicht; Daniel P Dowling

doi:10.1016/j.bbrc.2019.11.008

Structure and function of the two-component flavin-dependent methanesulfinate monooxygenase within bacterial sulfur assimilation

Biochem Biophys Res Commun. 2020 Jan 29;522(1):107-112. doi: 10.1016/j.bbrc.2019.11.008. Epub 2019 Nov 18.

Authors

Jess Soule¹, Andrew D Gnann¹, Reyaz Gonzalez¹, Mackenzie J Parker², Kylie C McKenna³, Son V Nguyen³, Ngan T Phan⁴, Denyce K Wicht⁵, Daniel P Dowling⁶

Affiliations

¹ Department of Chemistry, University of Massachusetts Boston, Boston, MA, 02125, USA.
² Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
³ Department of Chemistry and Biochemistry, Suffolk University, Boston, MA, 02108, USA.
⁴ Department of Chemistry, University of Massachusetts Boston, Boston, MA, 02125, USA; Department of Chemistry and Biochemistry, Suffolk University, Boston, MA, 02108, USA.
⁵ Department of Chemistry and Biochemistry, Suffolk University, Boston, MA, 02108, USA. Electronic address: dwicht@suffolk.edu.
⁶ Department of Chemistry, University of Massachusetts Boston, Boston, MA, 02125, USA. Electronic address: daniel.dowling@umb.edu.

PMID: 31753487
DOI: 10.1016/j.bbrc.2019.11.008

Abstract

Methyl sulfur compounds are a rich source of environmental sulfur for microorganisms, but their use requires redox systems. The bacterial sfn and msu operons contain two-component flavin-dependent monooxygenases for dimethylsulfone (DMSO₂) assimilation: SfnG converts DMSO₂ to methanesulfinate (MSI^-), and MsuD converts methanesulfonate (MS^-) to sulfite. However, the enzymatic oxidation of MSI^- to MS^- has not been demonstrated, and the function of the last enzyme of the msu operon (MsuC) is unresolved. We employed crystallographic and biochemical studies to identify the function of MsuC from Pseudomonas fluorescens. The crystal structure of MsuC adopts the acyl-CoA dehydrogenase fold with putative binding sites for flavin and MSI^-, and functional assays of MsuC in the presence of its oxidoreductase MsuE, FMN, and NADH confirm the enzymatic generation of MS^-. These studies reveal that MsuC converts MSI^- to MS^- in sulfite biosynthesis from DMSO₂.

Keywords: Crystal structure; Dimethylsulfide; Dimethylsulfone; Global sulfur cycle; Methanesulfinate; Methanesulfonate.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Acyl-CoA Dehydrogenase / metabolism
Bacterial Proteins / metabolism*
Binding Sites
Crystallography, X-Ray
Dimerization
Dimethyl Sulfoxide / chemistry
Flavins / chemistry
Magnetic Resonance Spectroscopy
Mesylates / chemistry
Molecular Docking Simulation
Oxidoreductases / metabolism
Oxygen / chemistry
Protein Structure, Secondary
Pseudomonas fluorescens / enzymology*
Structure-Activity Relationship
Sulfides / chemistry
Sulfones / chemistry
Sulfur / chemistry*
Thiophenes / chemistry

Substances

Bacterial Proteins
Flavins
Mesylates
Sulfides
Sulfones
Thiophenes
methanesulfonic acid
Sulfur
Oxidoreductases
Acyl-CoA Dehydrogenase
Oxygen
Dimethyl Sulfoxide
dibenzothiophene

Grants and funding

S10 OD021527/OD/NIH HHS/United States