Functional role of residues in the helix B ' region of cytochrome P4502B1
文献类型：期刊论文
| 作者 | Honma, W; Li, WH; Liu, H ; Scott, EE; Halpert, JR
|
| 刊名 | ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
 |
| 出版日期 | 2005-03-01 |
| 卷号 | 435期号:1页码:157-165 |
| 关键词 | cytochrome P450 monooxygenase site-directed mutagenesis |
| ISSN号 | 0003-9861 |
| DOI | 10.1016/j.abb.2004.12.014 |
| 文献子类 | Article |
| 英文摘要 | Comparison of several recently determined X-ray crystal structures of mammalian cytochrome P450 family, 2 enzymes suggests considerable movement of helix B' when ligands bind. To investigate the functional role of helix B' in P450 2B1, residues 100-109 were substituted with alanine and phenylalanine. Kinetic properties were examined with the typical 2B substrates 7-benzyloxyresorufin, 7-ethoxy-4-trifluoromethylcoumarin, benzphetamine, and testosterone. Several mutants showed 2- to 3-rold changes in 1 values and significant differences in catalytic efficiencies among the substrates examined, consistent with structural information suggesting that the helix B' region can adopt multiple conformations with different contact residues depending on the substrate. Homology modeling of P450 2B1 was performed based oil ail inhibitor-bound P450 2134 structure. and the docking analyses were consistent with experimental results. The findings suggest that residues in the helix B' region affect regio- and stereoselective oxidation in P450 family 2 enzymes as well as substrate entry. (C) 2004 Elsevier Inc. All rights reserved. |
| WOS关键词 | SITE-DIRECTED MUTAGENESIS ; SUBSTRATE RECOGNITION ; ANGSTROM RESOLUTION ; BINDING ; MONOOXYGENASE ; EXPRESSION ; SUBFAMILY ; P450BM-3 ; ACID ; 2B1 |
| 资助项目 | NIEHS NIH HHS[ES03619] ; NIEHS NIH HHS[ES06676] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000226782400017 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273897]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Honma, W |
| 作者单位 | 1.Univ Texas, Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Ctr Drug Discovery & Desig, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Honma, W,Li, WH,Liu, H,et al. Functional role of residues in the helix B ' region of cytochrome P4502B1[J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,2005,435(1):157-165. |
| APA | Honma, W,Li, WH,Liu, H,Scott, EE,&Halpert, JR.(2005).Functional role of residues in the helix B ' region of cytochrome P4502B1.ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,435(1),157-165. |
| MLA | Honma, W,et al."Functional role of residues in the helix B ' region of cytochrome P4502B1".ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 435.1(2005):157-165. |
入库方式： OAI收割
来源：上海药物研究所
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