title: Crystal structure of the catalytic domain of human ADAM33.
abstract: Adam33 is a putative asthma susceptibility gene encoding for a membrane-anchored metalloprotease belonging to the ADAM family. The ADAMs (a disintegrin and metalloprotease) are a family of glycoproteins implicated in cell-cell interactions, cell fusion, and cell signaling. We have determined the crystal structure of the Adam33 catalytic domain in complex with the inhibitor marimastat and the inhibitor-free form. The structures reveal the polypeptide fold and active site environment resembling that of other metalloproteases. The substrate-binding site contains unique features that allow the structure-based design of specific inhibitors of this enzyme.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA. peter.orth@spcorp.com
authors.forename: Peter
authors.initials: P
authors.lastname: Orth
authors.forename: Paul
authors.initials: P
authors.lastname: Reichert
authors.forename: Wenyan
authors.initials: W
authors.lastname: Wang
authors.forename: Winifred W
authors.initials: WW
authors.lastname: Prosise
authors.forename: Taisa
authors.initials: T
authors.lastname: Yarosh-Tomaine
authors.forename: Gerald
authors.initials: G
authors.lastname: Hammond
authors.forename: Richard N
authors.initials: RN
authors.lastname: Ingram
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.forename: Urooj A
authors.initials: UA
authors.lastname: Mirza
authors.forename: Jun
authors.initials: J
authors.lastname: Zou
authors.forename: Corey
authors.initials: C
authors.lastname: Strickland
authors.forename: S Shane
authors.initials: SS
authors.lastname: Taremi
authors.forename: Hung V
authors.initials: HV
authors.lastname: Le
authors.forename: Vincent
authors.initials: V
authors.lastname: Madison
mesh_terms: D051722:ADAM Proteins; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C100342:marimastat; D051722:ADAM Proteins; C450441:ADAM33 protein, human; D008666:Metalloendopeptidases