title: Tick histamine-binding proteins: lipocalins with a second binding cavity.
abstract: Tick histamine-binding proteins (HBPs) are lipocalins with two binding pockets. One of these binds histamine with a high affinity and is found at the position expected from other lipocalins, adjacent to the omega-loop at the open-end of the beta-barrel. A second binding cavity, which is a low-affinity site for histamine in one of the HBPs, is located at the end of the barrel that is closed off in other lipocalins. In order to create the second site, the 'closed-end' region has undergone a major reconstruction. Typical lipocalin characteristics, such as the 3(10) helix and a structural cluster of highly conserved residues, have been lost, while an alpha-helix now shields the cavity from the exterior. The prominence of acidic residues in the binding pockets is another distinctive characteristic of HBPs. Whereas most lipocalins have highly hydrophobic binding cavities designed to bind lipophilic compounds, HBPs have evolved to trap cationic, hydrophilic molecules.
authors.affiliation: CEH Institute of Virology and Environmental Microbiology, Oxford, UK. gcp@ceh.ac.uk
authors.forename: G C
authors.initials: GC
authors.lastname: Paesen
authors.forename: P L
authors.initials: PL
authors.lastname: Adams
authors.forename: P A
authors.initials: PA
authors.lastname: Nuttall
authors.forename: D L
authors.initials: DL
authors.lastname: Stuart
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003545:Cysteine / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011969:Receptors, Histamine H1 / Q000737:chemistry* / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013987:Ticks; D014364:Tryptophan / Q000378:metabolism
chemical_list: D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine; D014364:Tryptophan; D003545:Cysteine