title: Binding site differences revealed by crystal structures of Plasmodium falciparum and bovine acyl-CoA binding protein.
abstract: Acyl-CoA binding protein (ACBP) maintains a pool of fatty acyl-CoA molecules in the cell and plays a role in fatty acid metabolism. The biochemical properties of Plasmodium falciparum ACBP are described together with the 2.0 A resolution crystal structures of a P. falciparum ACBP-acyl-CoA complex and of bovine ACBP in two crystal forms. Overall, the bovine ACBP crystal structures are similar to the NMR structures published previously; however, the bovine and parasite ACBP structures are less similar. The parasite ACBP is shown to have a different ligand-binding pocket, leading to an acyl-CoA binding specificity different from that of bovine ACBP. Several non-conservative differences in residues that interact with the ligand were identified between the mammalian and parasite ACBPs. These, together with measured binding-specificity differences, suggest that there is a potential for the design of molecules that might selectively block the acyl-CoA binding site.
authors.affiliation: Wellcome Trust Biocentre, Department of Biochemistry University of Dundee, Scotland. dava@davapc1.bioch.dundee.ac.uk
authors.forename: D M
authors.initials: DM
authors.lastname: van Aalten
authors.forename: K G
authors.initials: KG
authors.lastname: Milne
authors.forename: J Y
authors.initials: JY
authors.lastname: Zou
authors.forename: G J
authors.initials: GJ
authors.lastname: Kleywegt
authors.forename: T
authors.initials: T
authors.lastname: Bergfors
authors.forename: M A
authors.initials: MA
authors.lastname: Ferguson
authors.forename: J
authors.initials: J
authors.lastname: Knudsen
authors.forename: T A
authors.initials: TA
authors.lastname: Jones
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D026261:Diazepam Binding Inhibitor; D015195:Drug Design; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D016415:Sequence Alignment; D055672:Static Electricity; D013379:Substrate Specificity
chemical_list: D001059:Apoproteins; D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D008024:Ligands