Crystal Structure of Nitrosomonas europaea Cytochrome c Peroxidase and the Structural Basis for Ligand Switching in Bacterial Di-heme Peroxidases
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- 作者：Hideaki Shimizu ; David J. Schuller ; William N. Lanzilotta ; M. Sundaramoorthy ; David M. Arciero ; Alan B. Hooper ; and Thomas L. Poulos
- 刊名：Biochemistry
- 出版年：2001
- 出版时间：November 13, 2001
- 年：2001
- 卷：40
- 期：45
- 页码：13483 - 13490
- 全文大小：751K
- 年卷期：v.40,no.45(November 13, 2001)
- ISSN：1520-4995
文摘
The crystal structure of the fully oxidized di-heme peroxidase from Nitrosomonas europaeahas been solved to a resolution of 1.80 Å and compared to the closely related enzyme from Pseudomonasaeruginosa. Both enzymes catalyze the peroxide-dependent oxidation of a protein electron donor such ascytochrome c. Electrons enter the enzyme through the high-potential heme followed by electron transferto the low-potential heme, the site of peroxide activation. Both enzymes form homodimers, each of whichfolds into two distinct heme domains. Each heme is held in place by thioether bonds between the hemevinyl groups and Cys residues. The high-potential heme in both enzymes has Met and His as axial hemeligands. In the Pseudomonas enzyme, the low-potential heme has two His residues as axial heme ligands[Fulop et al. (1995) Structure 3, 1225-1233]. Since the site of reaction with peroxide is the low-potentialheme, then one His ligand must first dissociate. In sharp contrast, the low-potential heme in theNitrosomonas enzyme already is in the "activated" state with only one His ligand and an open distal axialligation position available for reaction with peroxide. A comparison between the two enzymes illustratesthe range of conformational changes required to activate the Pseudomonas enzyme. This change involvesa large motion of a loop containing the dissociable His ligand from the heme pocket to the molecularsurface where it forms part of the dimer interface. Since the Nitrosomonas enzyme is in the active state,the structure provides some insights on residues involved in peroxide activation. Most importantly, a Gluresidue situated near the peroxide binding site could possibly serve as an acid-base catalytic group requiredfor cleavage of the peroxide O-O bond.