title: A novel haem-binding interface in the 22 kDa haem-binding protein p22HBP.
abstract: The 22 kDa haem-binding protein, p22HBP, is highly expressed in erythropoietic tissues and binds to a range of metallo- and non-metalloporphyrin molecules with similar affinities, suggesting a role in haem regulation or synthesis. We have determined the three-dimensional solution structure of p22HBP and mapped the porphyrin-binding site, which comprises a number of loops and a alpha-helix all located on a single face of the molecule. The structure of p22HBP is related to the bacterial multi-drug resistance protein BmrR, and is the first protein with this fold to be identified in eukaryotes. Strikingly, the porphyrin-binding site in p22HBP is located in a similar position to the drug-binding site of BmrR. These similarities suggest that the broad ligand specificity observed for both BmrR and p22HBP may result from a conserved ligand interaction mechanism. Taken together, these data suggest that the both the fold and its associated function, that of binding to a broad range of small hydrophobic molecules, are ancient, and have been adapted throughout evolution for a variety of purposes.
authors.affiliation: School of Molecular and Microbial Biosciences, University of Sydney, NSW 2006, Australia. dagell@usyd.edu.au
authors.forename: David A
authors.initials: DA
authors.lastname: Gell
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Westman
authors.forename: Daniel
authors.initials: D
authors.lastname: Gorman
authors.forename: Chukong
authors.initials: C
authors.lastname: Liew
authors.forename: John J
authors.initials: JJ
authors.lastname: Welch
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Weiss
authors.forename: Joel P
authors.initials: JP
authors.lastname: Mackay
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002942:Circular Dichroism; D006418:Heme / Q000378:metabolism*; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011166:Porphyrins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C098722:BmrR protein, bacteria; D002352:Carrier Proteins; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D011166:Porphyrins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D006418:Heme