title: 2 angstrom X-ray structure of adamalysin II complexed with a peptide phosphonate inhibitor adopting a retro-binding mode.
abstract: The search of reprolysin inhibitors offers the possibility of intervention against both matrixins and ADAMs. Here we report the crystal structure of the complex between adamalysin II, a member of the reprolysin family, and a phosphonate inhibitor modeled on an endogenous venom tripeptide. The inhibitor occupies the primed region of the cleavage site adopting a retro-binding mode. The phosphonate group ligates the zinc ion in an asymmetric bidentate mode and the adjacent Trp indole system partly fills the primary specificity subsite S1'. An adamalysin-based model of tumor necrosis factor-alpha-converting enzyme (TACE) reveals a smaller S1' pocket for this enzyme.
authors.affiliation: Ist. Strutturistica Chimica, CNR, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cirilli
authors.forename: C
authors.initials: C
authors.lastname: Gallina
authors.forename: E
authors.initials: E
authors.lastname: Gavuzzo
authors.forename: C
authors.initials: C
authors.lastname: Giordano
authors.forename: F X
authors.initials: FX
authors.lastname: Gomis-Rüth
authors.forename: B
authors.initials: B
authors.lastname: Gorini
authors.forename: L F
authors.initials: LF
authors.lastname: Kress
authors.forename: F
authors.initials: F
authors.lastname: Mazza
authors.forename: M P
authors.initials: MP
authors.lastname: Paradisi
authors.forename: G
authors.initials: G
authors.lastname: Pochetti
authors.forename: V
authors.initials: V
authors.lastname: Politi
mesh_terms: D003435:Crotalid Venoms / Q000378:metabolism; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry*; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D003435:Crotalid Venoms; D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; D010455:Peptides; D008666:Metalloendopeptidases; C028220:Crotalus adamanteus proteinase II