Structural Analysis of a Novel Cyclohexylamine Oxidase from Brevibacterium oxydans IH-35A
文献类型：期刊论文
| 作者 | Mirza, I. Ahmad3,4; Burk, David L.3,4; Xiong, Bing5 ; Iwaki, Hiroaki1,6; Hasegawa, Yoshie1,6; Grosse, Stephan7; Lau, Peter C. K.2,7,8,9; Berghuis, Albert M.3,4
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| 刊名 | PLOS ONE
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| 出版日期 | 2013-03-26 |
| 卷号 | 8期号:3 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0060072 |
| 文献子类 | Article |
| 英文摘要 | Cyclohexylamine oxidase (CHAO) is a flavoprotein first described in Brevibacterium oxydans strain IH-35A that carries out the initial step of the degradation of the industrial chemical cyclohexylamine to cyclohexanone. We have cloned and expressed in Escherichia coli the CHAO-encoding gene (chaA) from B. oxydans, purified CHAO and determined the structures of both the holoenzyme form of the enzyme and a product complex with cyclohexanone. CHAO is a 50 kDa monomer with a PHBH fold topology. It belongs to the flavin monooxygenase family of enzymes and exhibits high substrate specificity for alicyclic amines and sec-alkylamines. The overall structure is similar to that of other members of the flavin monooxygenase family, but lacks either of the C- or N-terminal extensions observed in these enzymes. Active site features of the flavin monooxygenase family are conserved in CHAO, including the characteristic aromatic cage. Differences in the orientations of residues of the CHAO aromatic cage result in a substrate-binding site that is more open than those of its structural relatives. Since CHAO has a buried hydrophobic active site with no obvious route for substrates and products, a random acceleration molecular dynamics simulation has been used to identify a potential egress route. The path identified includes an intermediate cavity and requires transient conformation changes in a shielding loop and a residue at the border of the substrate-binding cavity. These results provide a foundation for further studies with CHAO aimed at identifying features determining substrate specificity and for developing the biocatalytic potential of this enzyme. |
| WOS关键词 | EMPIRICAL FORCE-FIELD ; MONOAMINE-OXIDASE ; CRYSTAL-STRUCTURE ; MOLECULAR-DYNAMICS ; DIRECTED EVOLUTION ; NUCLEIC-ACIDS ; OXIDATION ; INHIBITORS ; SUBSTRATE ; INSIGHTS |
| 资助项目 | Natural Sciences and Engineering Research Council of Canada[RGPIN-183867] ; Canadian Institutes of Health Research[MOP-48370] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000317418500116 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277690]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Lau, Peter C. K. |
| 作者单位 | 1.Kansai Univ, ORDIST, Suita, Osaka, Japan; 2.FQRNT Ctr Green Chem & Catalysis, Montreal, PQ, Canada 3.McGill Univ, Dept Biochem, Montreal, PQ, Canada; 4.McGill Univ, Grp Rech Axe Struct Prot, Montreal, PQ, Canada; 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China; 6.Kansai Univ, Dept Life Sci & Biotechnol, Suita, Osaka, Japan; 7.Natl Res Council Canada, Montreal, PQ, Canada; 8.McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada; 9.McGill Univ, Dept Chem, Montreal, PQ, Canada; |
| 推荐引用方式 GB/T 7714 | Mirza, I. Ahmad,Burk, David L.,Xiong, Bing,et al. Structural Analysis of a Novel Cyclohexylamine Oxidase from Brevibacterium oxydans IH-35A[J]. PLOS ONE,2013,8(3). |
| APA | Mirza, I. Ahmad.,Burk, David L..,Xiong, Bing.,Iwaki, Hiroaki.,Hasegawa, Yoshie.,...&Berghuis, Albert M..(2013).Structural Analysis of a Novel Cyclohexylamine Oxidase from Brevibacterium oxydans IH-35A.PLOS ONE,8(3). |
| MLA | Mirza, I. Ahmad,et al."Structural Analysis of a Novel Cyclohexylamine Oxidase from Brevibacterium oxydans IH-35A".PLOS ONE 8.3(2013). |
入库方式： OAI收割
来源：上海药物研究所
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