Structural Determinants of an Insect beta-N-Acetyl-D-hexosaminidase Specialized as a Chitinolytic Enzyme
文献类型：期刊论文
| 作者 | Liu, Tian1; Zhang, Haitao3; Liu, Fengyi1; Wu, Qingyue1; Shen, Xu3,4 ; Yang, Qing1,2
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| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2011-02 |
| 卷号 | 286期号:6页码:4049-4058 |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.M110.184796 |
| 文献子类 | Article |
| 英文摘要 | beta-N-Acetyl-D-hexosaminidase has been postulated to have a specialized function. However, the structural basis of this specialization is not yet established. OfHex1, the enzyme from the Asian corn borer Ostrinia furnacalis (one of the most destructive pests) has previously been reported to function merely in chitin degradation. Here the vital role of OfHex1 during the pupation of O. furnacalis was revealed by RNA interference, and the crystal structures of OfHex1 and OfHex1 complexed with TMG-chitotriomycin were determined at 2.1 angstrom. The mechanism of selective inhibition by TMG-chitotriomycin was related to the existence of the +1 subsite at the active pocket of OfHex1 and a key residue, Trp(490), at this site. Mutation of Trp(490) to Ala led to a 2,277-fold decrease in sensitivity toward TMG-chitotriomycin as well as an 18-fold decrease in binding affinity for the substrate (GlcNAc)(2). Although the overall topology of the catalytic domain of OfHex1 shows a high similarity with the human and bacterial enzymes, OfHex1 is distinguished from these enzymes by large conformational changes linked to an "open-close" mechanism at the entrance of the active site, which is characterized by the "lid" residue, Trp(448). Mutation of Trp(448) to Ala or Phe resulted in a more than 1,000-fold loss in enzyme activity, due mainly to the effect on k(cat). The current work has increased our understanding of the structure-function relationship of OfHex1, shedding light on the structural basis that accounts for the specialized function of beta-N-acetyl-D-hexosaminidase as well as making the development of species-specific pesticides a likely reality. |
| WOS关键词 | SUBSTRATE-ASSISTED CATALYSIS ; LOBES GENE ENCODES ; TAY-SACHS-DISEASE ; MOLECULAR-CLONING ; OSTRINIA-FURNACALIS ; TMG-CHITOTRIOMYCIN ; CRYSTAL-STRUCTURE ; SANDHOFF-DISEASE ; PLASMA-MEMBRANE ; SF9 CELLS |
| 资助项目 | National Key Project for Basic Research[2010CB126100] ; National Key Project for Basic Research[2009CB918502] ; National Key Project for Basic Research[2010CB912501] ; Program for New Century Excellent Talents in University[00000000] ; East China University of Science and Technology, Shanghai, China[00000000] ; National Natural Science Foundation of China[10979072] ; Key New Drug Creation and Manufacturing Program[2009ZX09301-001] ; E-Institutes of Shanghai Municipal Education Commission[E09013] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000286975700003 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278615]  |
| 专题 | 药理学第三研究室 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 | Shen, Xu |
| 作者单位 | 1.Dalian Univ Technol, Dept Biosci & Biotechnol, Dalian 116024, Peoples R China; 2.E China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Shanghai Jiao Tong Univ, E Inst, Shanghai Municipal Educ Commiss, Sch Med, Shanghai 200025, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Tian,Zhang, Haitao,Liu, Fengyi,et al. Structural Determinants of an Insect beta-N-Acetyl-D-hexosaminidase Specialized as a Chitinolytic Enzyme[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(6):4049-4058. |
| APA | Liu, Tian,Zhang, Haitao,Liu, Fengyi,Wu, Qingyue,Shen, Xu,&Yang, Qing.(2011).Structural Determinants of an Insect beta-N-Acetyl-D-hexosaminidase Specialized as a Chitinolytic Enzyme.JOURNAL OF BIOLOGICAL CHEMISTRY,286(6),4049-4058. |
| MLA | Liu, Tian,et al."Structural Determinants of an Insect beta-N-Acetyl-D-hexosaminidase Specialized as a Chitinolytic Enzyme".JOURNAL OF BIOLOGICAL CHEMISTRY 286.6(2011):4049-4058. |
入库方式： OAI收割
来源：上海药物研究所
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