http://purl.uniprot.org/citations/15236578 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/15236578 | http://www.w3.org/2000/01/rdf-schema#comment | "Publication of the rhodopsin X-ray structure has facilitated the development of homology models of other G protein-coupled receptors. However, possible shifts of transmembrane (TM) alpha helices, expected variations in helical distortions, and differences in loop size necessitate experimental verification of these comparative models. To refine a rhodopsin-based homology model of the mu-opioid receptor (MOR), we experimentally determined structural-distance constraints from intrinsic and engineered metal-binding sites in the rat MOR. Investigating the relatively high intrinsic affinity of MOR for Zn(2+) (IC(50) approximately 30microM), we observed that mutation of His(319) (TM7) abolished Zn(2+) inhibition of ligand binding, while mutation of Asp(216) (extracellular loop 2) decreased the effect of Zn(2+), suggesting these residues participate in the intrinsic Zn(2+)-binding center of MOR. To verify the relative orientation of TM5 and TM6 and to examine whether a rhodopsin-like alpha aneurism is present in TM5, we engineered Zn(2+)-binding centers by mutating residues of TM5 and TM6 to Cys or His, making use of the native His(297) in TM6 as an additional Zn(2+)-coordination site. Inhibition of opioid ligand binding by Zn(2+) suggests that residues Ile(234) and Phe(237) in TM5 face the binding-site crevice and form a metal-binding center with His(297) and Val(300) in TM6. This observation is inconsistent with a rhodopsin-like structure, which would locate Ile(234) on the lipid-exposed side of TM5, too distant from other residues making up the Zn(2+)-binding site. Subsequent distance geometry refinement of the MOR model indicates that the rhodopsin-like alpha aneurism is likely absent in TM2 but present in TM5."xsd:string |
http://purl.uniprot.org/citations/15236578 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi036067r"xsd:string |
http://purl.uniprot.org/citations/15236578 | http://purl.uniprot.org/core/author | "Fowler C.B."xsd:string |
http://purl.uniprot.org/citations/15236578 | http://purl.uniprot.org/core/author | "Mosberg H.I."xsd:string |
http://purl.uniprot.org/citations/15236578 | http://purl.uniprot.org/core/author | "LeVine H."xsd:string |
http://purl.uniprot.org/citations/15236578 | http://purl.uniprot.org/core/author | "Pogozheva I.D."xsd:string |
http://purl.uniprot.org/citations/15236578 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
http://purl.uniprot.org/citations/15236578 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
http://purl.uniprot.org/citations/15236578 | http://purl.uniprot.org/core/pages | "8700-8710"xsd:string |
http://purl.uniprot.org/citations/15236578 | http://purl.uniprot.org/core/title | "Refinement of a homology model of the mu-opioid receptor using distance constraints from intrinsic and engineered zinc-binding sites."xsd:string |
http://purl.uniprot.org/citations/15236578 | http://purl.uniprot.org/core/volume | "43"xsd:string |
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