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Cooperativity and site selectivity in the ileal lipid binding protein.
Turpin, Eleanor R; Fang, Huey-Jen; Thomas, Neil R; Hirst, Jonathan D.
Afiliación
  • Turpin ER; School of Chemistry, University of Nottingham , University Park, Nottingham NG7 2RD, United Kingdom.
Biochemistry ; 52(27): 4723-33, 2013 Jul 09.
Article en En | MEDLINE | ID: mdl-23758264
The ileal lipid binding protein (ILBP or I-BABP) binds bile salts with positive cooperativity and has unusual site selectivity, whereby cholic acid binds preferentially in one site and chenodeoxycholic in another, despite both sites having an affinity for both ligands and the ligands only differing by a single hydroxyl group. Previous studies of the human variant have assumed that the ligand/protein binding ratio is 2:1, but we show, using electrospray ionization mass spectroscopy, that human ILBP binds bile acids with a 3:1 ratio, even at low protein and ligand concentrations. Docking calculations and molecular dynamics (MD) simulations identify an allosterically active binding site on the protein exterior that induces a change from a closed conformation to an open one, characterized by a movement of one of the α-helices by ~10° with respect to the ß-clam shell. Additional independent MD simulations of several hundred nanoseconds implicate the change between conformations in the mechanisms of both cooperativity and ligand site selectivity.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Ácidos y Sales Biliares / Transportadores de Anión Orgánico Sodio-Dependiente / Simportadores Límite: Humans Idioma: En Revista: Biochemistry Año: 2013 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Ácidos y Sales Biliares / Transportadores de Anión Orgánico Sodio-Dependiente / Simportadores Límite: Humans Idioma: En Revista: Biochemistry Año: 2013 Tipo del documento: Article País de afiliación: Reino Unido