Structural Basis for Novel -Regioselective Heme Oxygenation in the Opportunistic Pathogen Pseudomonas aeruginosa
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- 作者：Jonathan Friedman ; Latesh Lad ; Huiying Li ; Angela Wilks ; and Thomas L. Poulos
- 刊名：Biochemistry
- 出版年：2004
- 出版时间：May 11, 2004
- 年：2004
- 卷：43
- 期：18
- 页码：5239 - 5245
- 全文大小：529K
- 年卷期：v.43,no.18(May 11, 2004)
- ISSN：1520-4995
文摘
The Gram-negative bacterium Pseudomonas aeruginosa contains a heme oxygenase (pa-HO)that primarily oxygenates the 
-meso heme carbon [Caignan, G. A., Deshmukh, R., Wilks, A., Zeng, Y.,Huang, H. W., Moenne-Loccoz, P., Bunce, R. A., Eastman, M. A., and Rivera, M. (2002) J. Am. Chem.Soc. 124, 14879-14892]. This differs from other previously characterized heme oxygenases, which displayregioselectivity for the 
-meso heme carbon. Here we report the crystal structure of pa-HO at 1.60 Åresolution and compare it to the 1.50 Å structure of nm-HO from Neisseria meningitidis [Schuller, D. J.,Zhu, W., Stojiljkovic, I., Wilks, A., and Poulos, T. L. (2001) Biochemistry 40, 11552-11558]. The crystalstructure of pa-HO maintains the same overall fold as other bacterial and mammalian heme oxygenases,including a conserved network of hydrogen-bonded solvent molecules important for dioxygen activation.The novel -regioselectivity of heme oxygenation observed by pa-HO is due to the heme being rotatedby ~100
, which places the -meso heme carbon in the same position as the -meso heme carbon inother heme oxygenases. The main interaction in pa-HO that stabilizes the unique heme orientation is asalt bridge between Lys132 and the heme 7-propionate, as well as hydrophobic contacts involving Leu29,Val33, and Phe189 with the heme methyl and vinyl groups.
-meso heme carbon [Caignan, G. A., Deshmukh, R., Wilks, A., Zeng, Y.,Huang, H. W., Moenne-Loccoz, P., Bunce, R. A., Eastman, M. A., and Rivera, M. (2002) J. Am. Chem.Soc. 124, 14879-14892]. This differs from other previously characterized heme oxygenases, which displayregioselectivity for the -meso heme carbon. Here we report the crystal structure of pa-HO at 1.60 Åresolution and compare it to the 1.50 Å structure of nm-HO from Neisseria meningitidis [Schuller, D. J.,Zhu, W., Stojiljkovic, I., Wilks, A., and Poulos, T. L. (2001) Biochemistry 40, 11552-11558]. The crystalstructure of pa-HO maintains the same overall fold as other bacterial and mammalian heme oxygenases,including a conserved network of hydrogen-bonded solvent molecules important for dioxygen activation.The novel -regioselectivity of heme oxygenation observed by pa-HO is due to the heme being rotatedby ~100, which places the -meso heme carbon in the same position as the -meso heme carbon inother heme oxygenases. The main interaction in pa-HO that stabilizes the unique heme orientation is asalt bridge between Lys132 and the heme 7-propionate, as well as hydrophobic contacts involving Leu29,Val33, and Phe189 with the heme methyl and vinyl groups.