...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >An aspartate and a water molecule mediate efficient acid-base catalysis in a tailored antibody pocket
【24h】

An aspartate and a water molecule mediate efficient acid-base catalysis in a tailored antibody pocket

机译：天冬氨酸和水分子在定制的抗体袋中介导有效的酸碱催化

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Design of catalysts featuring multiple functional groups is a desirable, yet formidable goal. Antibody 13G5, which accelerates the cleavage of unactivated benzisoxazoles, is one of few artificial enzymes that harness an acid and a base to achieve efficient proton transfer. X-ray structures of the Fab-hapten complexes of wild-type 13G5 and active-site variants now afford detailed insights into its mechanism. The parent antibody preorganizes Asp~(H35) and Glu~(L34) to abstract a proton from substrate and to orient a water molecule for leaving group stabilization, respectively. Remodeling the environment of the hydrogen bond donor with a compensatory network of ordered waters, as seen in the Glu~(L34) to alanine mutant, leads to an impressive 10~9-fold rate acceleration over the nonenzymatic reaction with acetate, illustrating the utility of buried water molecules in bif unctional catalysis. Generalization of these design principles may aid in creation of catalysts for other important chemical transformations.
机译：具有多个官能团的催化剂的设计是理想的，但也是一个艰巨的目标。抗体13G5可以加速未活化的苯并异恶唑的裂解，是利用酸和碱实现有效质子转移的少数人工酶之一。野生型13G5和活性位点变异的Fab-半抗原复合物的X射线结构现在提供了对其机制的详细了解。亲本抗体会预先组织Asp_（H35）和Glu_（L34），以从底物中提取质子，并定向水分子以保持基团稳定。用有序水的补偿网络重整氢键供体的环境，如在Glu〜（L34）到丙氨酸突变体中所见，比起用乙酸盐进行的非酶反应，具有令人印象深刻的10〜9倍速率加速，说明了其实用性。功能催化中埋藏的水分子的分布这些设计原理的一般化可能有助于创建其他重要化学转化的催化剂。

著录项

  • 来源
  • 作者

    Erik W. Debler; Roger Mueller; Donald Hilvert; Ian A. Wilson;

  • 作者单位

    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 Laboratory of Cell Biology, Howard Hughes Medical Institute, 1230York Avenue, Rockefeller University, New York, NY 10065;

    Laboratorium fuer Organische Chemie, ETH Zuerich, CH-8093 Zuerich, Switzerland Munich Center for Integrated Protein Science (CIPSM) at the Department Chemie, Technische Universitaet Muenchen, D-85747 Garching, Germany;

    Laboratorium fuer Organische Chemie, ETH Zuerich, CH-8093 Zuerich, Switzerland;

    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    catalytic antibody; crystal structure; enzyme design; enzyme mechanism; proton transfer;

    机译：催化抗体晶体结构酶设计;酶机制质子转移;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号