title: Active site targeting of hedgehog precursor protein with phenylarsine oxide.
abstract: Hedgehog proteins, signaling molecules implicated in human embryo development and cancer, can be inhibited at the stage of autoprocessing by the trivalent arsenical phenyl arsine oxide (PhAs(III) ). The interaction (apparent Ki , 4 × 10(-7) M) is characterized by an optical binding assay and by NMR spectroscopy. PhAs(III) appears to be the first validated inhibitor of hedgehog autoprocessing, which is unique to hedgehog proteins and essential for biological activity.
authors.affiliation: Chemistry Department, Binghamton University, 4400 Vestal Parkway East, Binghamton, New York (USA).
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Owen
authors.forename: Xie Jian
authors.initials: XJ
authors.lastname: Xie
authors.forename: Benjamin
authors.initials: B
authors.lastname: Laraway
authors.forename: George
authors.initials: G
authors.lastname: Ngoje
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.forename: Brian P
authors.initials: BP
authors.lastname: Callahan
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000737:chemistry*; D020134:Catalytic Domain; D002784:Cholesterol / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding; D011498:Protein Precursors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D001152:Arsenicals; D053823:Hedgehog Proteins; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; C029341:oxophenylarsine; D002784:Cholesterol
keywords: active-site probe; arsenic; autoprocessing; cholesterol; hedgehog