Pressure-Induced Deformation of the Cytochrome P450cam Active Site
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- 作者：Richard A. Tschirret-Guth ; Gaston Hui Bon Hoa ; and Paul R. Ortiz de Montellano
- 刊名：Journal of the American Chemical Society
- 出版年：1998
- 出版时间：April 22, 1998
- 年：1998
- 卷：120
- 期：15
- 页码：3590 - 3596
- 全文大小：158K
- 年卷期：v.120,no.15(April 22, 1998)
- ISSN：1520-5126
文摘
The reaction of cytochrome P450cam with aryldiazenes(ArN=NH) yields 
-bonded iron-aryl (Fe-aryl) complexes. Oxidation of the complexes causes regioselectivemigration of the aryl group from the ironto the porphyrin nitrogens. The influence of high pressure on theformation and rearrangement of the Fe-aryl complexes is reported here. The natural logarithm of the rateof formation of the Fe-phenyl complexdecreases linearly with pressure with a volume of activation of 38.2 mLmol-1. The Fe-phenyl,Fe-(2-naphthyl), and Fe-(p-biphenyl) complexes are stable atatmospheric pressure but decompose in a pressure-dependent manner at pressures above 1500 (Fe-phenyl) or 2500 bar(Fe-(2-naphthyl) or Fe-(p-biphenyl)).This pressure-induced decomposition results in formation of theN-arylprotoporphyrin IX adducts. TheN-arylporphyrin regioisomer patterns obtained by pressure-induced migrationof the aryl groups(NB:NA:NC:ND,Ph,10:14:33:43; 2-naphthyl, 12:13:37:38; p-biphenyl,15:15:33:37) differ from those obtained by oxidation oftheP450cam Fe-aryl complexes at atmospheric pressure (Ph,00:05:25:70; 2-naphthyl, 00:00:100:00;p-biphenyl,00:14:40:46). Preincubation of P450cam at elevatedpressure followed by decompression, Fe-phenyl complexformation, and oxidative shift yields the same N-phenyl regioisomerratio as the pressure-induced shift. Thethree principal findings of this study are that (a) theiron-to-nitrogen migration of the aryl group can bepromotedby pressure, (b) differential distortion of the P450camactive site by high pressure causes small displacementsof the I-helix and residues associated with the substrate accesschannel, and (c) pressure causes a subtle structuralchange in the P450cam active site that persists atatmospheric pressure.
-bonded iron-aryl (Fe-aryl) complexes. Oxidation of the complexes causes regioselectivemigration of the aryl group from the ironto the porphyrin nitrogens. The influence of high pressure on theformation and rearrangement of the Fe-aryl complexes is reported here. The natural logarithm of the rateof formation of the Fe-phenyl complexdecreases linearly with pressure with a volume of activation of 38.2 mLmol-1. The Fe-phenyl,Fe-(2-naphthyl), and Fe-(p-biphenyl) complexes are stable atatmospheric pressure but decompose in a pressure-dependent manner at pressures above 1500 (Fe-phenyl) or 2500 bar(Fe-(2-naphthyl) or Fe-(p-biphenyl)).This pressure-induced decomposition results in formation of theN-arylprotoporphyrin IX adducts. TheN-arylporphyrin regioisomer patterns obtained by pressure-induced migrationof the aryl groups(NB:NA:NC:ND,Ph,10:14:33:43; 2-naphthyl, 12:13:37:38; p-biphenyl,15:15:33:37) differ from those obtained by oxidation oftheP450cam Fe-aryl complexes at atmospheric pressure (Ph,00:05:25:70; 2-naphthyl, 00:00:100:00;p-biphenyl,00:14:40:46). Preincubation of P450cam at elevatedpressure followed by decompression, Fe-phenyl complexformation, and oxidative shift yields the same N-phenyl regioisomerratio as the pressure-induced shift. Thethree principal findings of this study are that (a) theiron-to-nitrogen migration of the aryl group can bepromotedby pressure, (b) differential distortion of the P450camactive site by high pressure causes small displacementsof the I-helix and residues associated with the substrate accesschannel, and (c) pressure causes a subtle structuralchange in the P450cam active site that persists atatmospheric pressure.