CRYSTAL STRUCTURE DETERMINATION OF CATALYTIC ANTIBODIES

催化抗体的晶体结构测定

基本信息

  • 批准号:
    2887112
  • 负责人:
  • 金额:
    $ 6.21万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1997
  • 资助国家:
    美国
  • 起止时间:
    1997-04-01 至 1999-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: Structure-function studies of catalytic antibodies are to focus on three systems. (1) The antibody 48G7 which was elicited to a phosphonate transition-state (TS) analogue and catalyzes the hydrolysis of the corresponding esters and carbonates. This system represents one of the simplest and most prevalent antibody-catalyzed reactions to study transition state stabilization and catalysis. Moreover, the germline genes have been cloned and expressed, permitting the study of the immunological evolution of catalysis. The functional effects of affinity maturation on TS analogue binding and catalysis can be analyzed and interpreted in terms of the three-dimensional structures of both the mature (48G7) and germline antibodies. In addition, a high level expression system in E. coli will allow a systematic mutagenesis study of both the active site and somatically mutated residues. (2) The antibody AZ-28 which was elicited against a chairlike TS analogue and catalyzes the corresponding oxy-Cope rearrangement. There are virtually no enzymes that catalyze such pericyclic rearrangements with the exception of chorismate mutase, the mechanism of which remains unclear despite extensive structural and mechanistic studies. Consequently, detailed structure-function studies of this biological catalyst may shed insight into the requirements for catalysis of the chemical transformation. Moreover, the availability of a family of antibodies that catalyze this unimolecular reaction may help to elucidate those factors essential for activity. (3) The antibody 28B4.2 which catalyzes the oxygenation reaction of a thioether to the corresponding sulfoxide. This was the first biological catalyst to use an abiological "cofactor" for activity, i.e. a periodate ion, in place of the heme and flavin cofactors used by the corresponding enzymes. The kcat values for the antibody and enzymes are comparable, suggesting that this strategy may allow the replacement of expensive cofactors with inexpensive chemical cofactors. A detailed understanding of the structure and mechanism of this antibody and the relationship of the active site structure to hapten structure may suggest generalizations and may allow engineering of antibodies with enhanced stereoselectivities or may permit modification of the antibody to other reactions such as disulfide bond formation.
描述:催化抗体的结构-功能研究

项目成果

期刊论文数量(0)
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RAYMOND C STEVENS其他文献

RAYMOND C STEVENS的其他文献

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{{ truncateString('RAYMOND C STEVENS', 18)}}的其他基金

Platform for Structure-Function Studies of Adhesion GPCRs implicated in Cancer
与癌症相关的粘附 GPCR 的结构功能研究平台
  • 批准号:
    8926375
  • 财政年份:
    2015
  • 资助金额:
    $ 6.21万
  • 项目类别:
Structural Diversity of Botulinum Toxin
肉毒杆菌毒素的结构多样性
  • 批准号:
    8260255
  • 财政年份:
    2011
  • 资助金额:
    $ 6.21万
  • 项目类别:
CHARACTERIZATION OF MEMBRANE PROTEIN COMPLEXES
膜蛋白复合物的表征
  • 批准号:
    8362472
  • 财政年份:
    2011
  • 资助金额:
    $ 6.21万
  • 项目类别:
RAY STEVENS PRT TIME
雷·史蒂文斯 PRT 时间
  • 批准号:
    8362034
  • 财政年份:
    2011
  • 资助金额:
    $ 6.21万
  • 项目类别:
CHARACTERIZATION OF MEMBRANE PROTEIN COMPLEXES
膜蛋白复合物的表征
  • 批准号:
    8169696
  • 财政年份:
    2010
  • 资助金额:
    $ 6.21万
  • 项目类别:
GPCR Network
GPCR网络
  • 批准号:
    8324098
  • 财政年份:
    2010
  • 资助金额:
    $ 6.21万
  • 项目类别:
GPCR Network
GPCR网络
  • 批准号:
    8289728
  • 财政年份:
    2010
  • 资助金额:
    $ 6.21万
  • 项目类别:
GPCR Network
GPCR网络
  • 批准号:
    8240577
  • 财政年份:
    2010
  • 资助金额:
    $ 6.21万
  • 项目类别:
GPCR Network
GPCR网络
  • 批准号:
    8501563
  • 财政年份:
    2010
  • 资助金额:
    $ 6.21万
  • 项目类别:
Management Core
管理核心
  • 批准号:
    8152444
  • 财政年份:
    2010
  • 资助金额:
    $ 6.21万
  • 项目类别:

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ABZYME CATALYZED SITE-SPECIFIC ACYLATION OF PROTEINS
ABZYME 催化的蛋白质位点特异性酰化
  • 批准号:
    2608715
  • 财政年份:
    1997
  • 资助金额:
    $ 6.21万
  • 项目类别:
ABZYME CATALYZED SITE-SPECIFIC ACYLATION OF PROTEINS
ABZYME 催化的蛋白质位点特异性酰化
  • 批准号:
    2173187
  • 财政年份:
    1997
  • 资助金额:
    $ 6.21万
  • 项目类别:
MOLECULAR GENETICS TO STUDY AND IMPROVE ABZYME FUNCTION
利用分子遗传学研究和改善 ABZYME 功能
  • 批准号:
    3044370
  • 财政年份:
    1989
  • 资助金额:
    $ 6.21万
  • 项目类别:
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