title: Small molecule designed to target metal binding site in the alpha2I domain inhibits integrin function.
abstract: Integrin alpha2beta1 is a potential target molecule in drug development. We have established "design" criteria for molecules that bind to the "closed" conformation of alpha2I domain via Mg(2+) in MIDAS (metal ion dependent adhesion site) while simultaneously forming interactions with neighboring amino acid residues. Specific tetracyclic Streptomyces products belonging to the group of aromatic polyketides fulfill our criteria and inhibit alpha2beta1 integrin. All previously described inhibitors of alphaI domain integrins act in an allosteric manner.
authors: Department of Biochemistry and Food Chemistry, University of Turku, FI-20014 Turku, Finland.
authors: Jarmo
authors: J
authors: Käpylä
authors: Olli T
authors: OT
authors: Pentikäinen
authors: Tommi
authors: T
authors: Nyrönen
authors: Liisa
authors: L
authors: Nissinen
authors: Sanna
authors: S
authors: Lassander
authors: Johanna
authors: J
authors: Jokinen
authors: Matti
authors: M
authors: Lahti
authors: Anne
authors: A
authors: Marjamäki
authors: Mark S
authors: MS
authors: Johnson
authors: Jyrki
authors: J
authors: Heino
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002413:Cations, Divalent; D002448:Cell Adhesion; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013302:Streptomyces / Q000737:chemistry; D013754:Tetracyclines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D002413:Cations, Divalent; D016023:Integrins; D013754:Tetracyclines; D008274:Magnesium