Mutagenesis and molecular dynamics suggest structural and functional roles for residues in the N-terminal portion of the cytochrome P4502B1Ihelix
文献类型：期刊论文
| 作者 | Scott, EE; Liu, H ; He, YQ; Li, WH; Halpert, JR
|
| 刊名 | ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
 |
| 出版日期 | 2004-03-15 |
| 卷号 | 423期号:2页码:266-276 |
| 关键词 | cytochrome p450 monooxygenase site-directed mutagenesis steered molecular dynamics substrate access |
| ISSN号 | 0003-9861 |
| DOI | 10.1016/j.abb.2003.12.035 |
| 文献子类 | Article |
| 英文摘要 | To investigate their potential roles in ligand access, binding, and subsequent metabolism, residues in the N-terminal portion of the cytochrome P450 2B1 I helix were mutated to alanine and phenylalanine. Of the 18 mutants from E286 to S294 only 7 yielded holoprotein in an Escherichia coli expression system. Substitutions at positions 289, 290, 292, and 294 caused greater than or equal to 2-fold changes in k(cat) and/or K-m for two or more of the 2B1 substrates examined, testosterone, 7-ethoxy-4-trifluoromethylcoumarin, 7-benzyloxyresorufin, and benzphetamine. 1290 substitutions had the largest effects on steady-state parameters for three substrates and increased benzphetamine affinity. Steered molecular dynamics simulations of testosterone egress along the I helix identified hydrophobic interactions with 1290, L293, and S294 and water bridges to E286 and S294. Sensitivity of holoprotein formation to substitution and effects on substrate binding and metabolism suggest structural and functional roles for residues in the N-terminus of the cytochrome P450 2B1 I helix. (C) 2004 Elsevier Inc. All rights reserved. |
| WOS关键词 | BURIED ACTIVE-SITE ; PARTICLE MESH EWALD ; CRYSTAL-STRUCTURE ; DIRECTED MUTAGENESIS ; ANGSTROM RESOLUTION ; SUBSTRATE-BINDING ; PRODUCTS EXIT ; P450 ; ACID ; COMPLEX |
| 资助项目 | NIGMS NIH HHS[GM20674] ; 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:000220164100004 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/274104]  |
| 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 | Scott, EE |
| 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,Ctr Drug Discovery & Design, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Scott, EE,Liu, H,He, YQ,et al. Mutagenesis and molecular dynamics suggest structural and functional roles for residues in the N-terminal portion of the cytochrome P4502B1Ihelix[J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,2004,423(2):266-276. |
| APA | Scott, EE,Liu, H,He, YQ,Li, WH,&Halpert, JR.(2004).Mutagenesis and molecular dynamics suggest structural and functional roles for residues in the N-terminal portion of the cytochrome P4502B1Ihelix.ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS,423(2),266-276. |
| MLA | Scott, EE,et al."Mutagenesis and molecular dynamics suggest structural and functional roles for residues in the N-terminal portion of the cytochrome P4502B1Ihelix".ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 423.2(2004):266-276. |
入库方式： OAI收割
来源：上海药物研究所
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