title: QM/MM model of the mouse olfactory receptor MOR244-3 validated by site-directed mutagenesis experiments.
abstract: Understanding structure/function relationships of olfactory receptors is challenging due to the lack of x-ray structural models. Here, we introduce a QM/MM model of the mouse olfactory receptor MOR244-3, responsive to organosulfur odorants such as (methylthio)methanethiol. The binding site consists of a copper ion bound to the heteroatoms of amino-acid residues H105, C109, and N202. The model is consistent with site-directed mutagenesis experiments and biochemical measurements of the receptor activation, and thus provides a valuable framework for further studies of the sense of smell at the molecular level.
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut. Electronic address: sivakumar.sekharan@yale.edu.
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Sekharan
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut; Chemistry Department, Brookhaven National Laboratory, Upton, New York. Electronic address: mzertem@bnl.gov.
authors.forename: Mehmed Z
authors.initials: MZ
authors.lastname: Ertem
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China; Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine/Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, Shanghai, P. R. China. Electronic address: hanyizhuang@sjtu.edu.cn.
authors.forename: Hanyi
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, Albany, New York.
authors.forename: Eric
authors.initials: E
authors.lastname: Block
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina; Department of Neurobiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsunami
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
authors.forename: Ruina
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Wei
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut. Electronic address: victor.batista@yale.edu.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Batista
mesh_terms: D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D003300:Copper / Q000737:chemistry; D006801:Humans; D007477:Ions / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D043585:Receptor, Muscarinic M2 / Q000737:chemistry; D018035:Receptors, Odorant / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D007477:Ions; C571731:MOR244-3 protein, mouse; C498563:Olfr256 protein, mouse; D043585:Receptor, Muscarinic M2; D018035:Receptors, Odorant; D014867:Water; D003300:Copper