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 α-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. © 2006 Elsevier Ltd. All rights reserved.

Item Type:	Refereed Article
Research Division:	Biological Sciences
Research Group:	Biochemistry and cell biology
Research Field:	Structural biology (incl. macromolecular modelling)
Objective Division:	Expanding Knowledge
Objective Group:	Expanding knowledge
Objective Field:	Expanding knowledge in the biological sciences
UTAS Author:	Gell, DA (Dr David Gell)
ID Code:	64535
Year Published:	2006
Web of Science® Times Cited:	7
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2010-08-12
Last Modified:	2011-07-29
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