title: Genetically encoded photo-cross-linkers map the binding site of an allosteric drug on a G protein-coupled receptor.
abstract: G protein-coupled receptors (GPCRs) are dynamic membrane proteins that bind extracellular molecules to transduce signals. Although GPCRs represent the largest class of therapeutic targets, only a small percentage of their ligand-binding sites are precisely defined. Here we describe the novel application of targeted photo-cross-linking using unnatural amino acids to obtain structural information about the allosteric binding site of a small molecule drug, the CCR5-targeted HIV-1 co-receptor blocker maraviroc.
authors.forename: Amy
authors.initials: A
authors.lastname: Grunbeck
authors.forename: Thomas
authors.initials: T
authors.lastname: Huber
authors.forename: Ravinder
authors.initials: R
authors.lastname: Abrol
authors.forename: Bartosz
authors.initials: B
authors.lastname: Trzaskowski
authors.forename: William A
authors.initials: WA
authors.lastname: Goddard
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Sakmar
mesh_terms: D000495:Allosteric Site; D065100:CCR5 Receptor Antagonists; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology*; D057809:HEK293 Cells; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D000077592:Maraviroc; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D019713:Receptors, CCR5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology*; D014466:Ultraviolet Rays; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D065100:CCR5 Receptor Antagonists; D003432:Cross-Linking Reagents; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D019713:Receptors, CCR5; D014230:Triazoles; D000077592:Maraviroc