A Novel Haem-binding Interface in the 22 kDa Haem-binding Protein p22HBP
- 作者：David A. Gell ; Belinda J. Westman ; Daniel Gorman ; ChuKong Liew ; John J. Welch ; Mitchell J. Weiss and Joel P. Mackay
- 关键词：protein structure ; NMR ; haem ; p22HBP ; haem-binding protein
- 刊名：Journal of Molecular Biology
- 出版年：2006
- 期刊代码：102_00222836
- 类别：imm
- 出版时间：15 September 2006
- 卷：362
- 期：2
- 页码：287-297
- 文件大小：1063 K
摘要
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.