Looking in New Directions for Origins and Cryptic Mechanisms of Enzyme Catalysis
Looking in New Directions for Origins and Cryptic Mechanisms of Enzyme Catalysis
批准号:
10379311
负责人:
JUDITH P KLINMAN
金额:
$69.02万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
未结题
起止时间:
2016-04-01 至 2026-04-30
关键词:
Active SitesAddressAntibioticsAreaBiochemicalBiologicalCatalysisChemistryCouplingDevelopmentDrug TargetingEnzymesEventFamilyHandHumanHydrogenKnowledgeMethodologyMotionPQQ CofactorPathway interactionsPeptidesPost-Translational Protein ProcessingPropertyProteinsReactionRibosomesVitaminscatalystcofactordesignenzyme activityenzyme mechanismenzyme structurenovelnovel strategiesprotein functionprototypetemporal measurement
中文摘要
项目总结:
这个项目的重点是了解酶的物理和机械性质。
它们精致的功能。近年来,蛋白质运动被认为是实现
极快地催化酶活性部位的键断裂事件。空间和空间分析的方法
这种蛋白质运动的时间分辨率是使用催化蛋白质运动的酶原型开发的
氢和甲基转移反应。这些研究现在正在扩展到蒂姆·巴尔家族
代表已知酶结构的10%的酶,并催化7个已知EC类别中的5个。有了这个
有了现有的知识,蛋白质重新设计、从头设计和药物靶向的新方法就出现了。一秒钟
生物催化领域的新兴领域涉及到已经被
在核糖体中合成。一种结构和生化探针的组合正在解决这个谜团
产生细菌辅因子和维生素、吡咯喹啉醌的途径。作为一个数字的结果
在最近的突破性观察中,该途径中的每个催化剂现在都可以详细地
机械学研究。这些酶在人类中几乎没有先例,使PQQ途径成为
抗生素开发的可能新目标。
英文摘要
Project Summary:
This project is focused on understanding the physical and mechanistic properties of enzymes that underlie
their exquisite function. In recent years, protein motions have been implicated as essential to achieve an
extremely rapid catalysis of bond cleavage events at enzyme active sites. Methodology for the spatial and
temporal resolution of such protein motions has been developed using enzyme prototypes that catalyze
hydrogen and methyl transfer reactions. These studies are now being extended to the TIM barrel family of
enzymes that represent 10% of known enzyme structures and catalyze 5 out of 7 known EC classes. With this
knowledge in hand, new approaches arise for protein redesign, de novo design and drug targeting. A second
emerging area in biological catalysis concerns the post-translational modification of peptides that have been
synthesized at the ribosome. A combination of structural and biochemical probes is addressing the enigmatic
pathway that produces the bacterial cofactor and vitamin, pyrroloquinoline quinone. As the result of a number
of recent breakthrough observations, each of the catalysts within the pathway is now amenable for detailed
mechanistic study. These enzymes have little or no precedence in humans, making the PQQ pathway a
possible new target for antibiotic development.
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会议论文
Looking in New Directions for Origins and Cryptic Mechanisms of Enzyme Catalysis
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批准号:10166437
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项目类别:
-
资助金额:$75.91万
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财政年份:2016
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负责人:JUDITH P KLINMAN
-
依托单位:
Looking in New Directions for Origins and Cryptic Mechanisms of Enzyme Catalysis
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批准号:9251860
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项目类别:
-
资助金额:$79.58万
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财政年份:2016
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负责人:JUDITH P KLINMAN
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依托单位:
Looking in New Directions for Origins and Cryptic Mechanisms of Enzyme Catalysis
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批准号:9892015
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项目类别:
-
资助金额:$79.58万
-
财政年份:2016
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负责人:JUDITH P KLINMAN
-
依托单位:
Looking in New Directions for Origins and Cryptic Mechanisms of Enzyme Catalysis
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批准号:10636781
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项目类别:
-
资助金额:$69.02万
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财政年份:2016
-
负责人:JUDITH P KLINMAN
-
依托单位:
Principles of C-H and O2 Activation
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批准号:7937495
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项目类别:
-
资助金额:$10.96万
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财政年份:2009
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负责人:JUDITH P KLINMAN
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依托单位:
Gordon Research Conference on Protein-Derived Cofactors
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批准号:6455540
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项目类别:
-
资助金额:$0.2万
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财政年份:2002
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负责人:JUDITH P KLINMAN
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依托单位:
CHARACTERIZATION OF ACTIVE SITE COFACTOR OF BOVINE AORTA LYSYL OXIDASE
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批准号:6251424
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项目类别:
-
资助金额:$1.1万
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财政年份:1997
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负责人:JUDITH P KLINMAN
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依托单位:
QUINOENZYMES--BIOGENESIS STRUCTURE AND FUNCTION
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批准号:2179739
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项目类别:
-
资助金额:$27.3万
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财政年份:1988
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负责人:JUDITH P KLINMAN
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依托单位:
QUINOENZYMES: BIOGENESIS, STRUCTURE AND FUNCTION
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批准号:6041722
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项目类别:
-
资助金额:$40.97万
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财政年份:1988
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负责人:JUDITH P KLINMAN
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依托单位:
PROBES OF STRUCTURE AND MECHANISM IN COPPER AMINE
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批准号:3296145
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项目类别:
-
资助金额:$16.03万
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财政年份:1988
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负责人:JUDITH P KLINMAN
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依托单位:
PROBES OF STRUCTURE & MECHANISM IN COPPER AMINE OXIDASES
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批准号:3296146
-
项目类别:
-
资助金额:$18.9万
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财政年份:1988
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负责人:JUDITH P KLINMAN
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依托单位:
Protein and Peptide Derived Cofactors
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批准号:8826130
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项目类别:
-
资助金额:$38.43万
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财政年份:1988
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负责人:JUDITH P KLINMAN
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依托单位:
QUINOENZYMES--BIOGENESIS STRUCTURE AND FUNCTION
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批准号:2654950
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项目类别:
-
资助金额:$25.23万
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财政年份:1988
-
负责人:JUDITH P KLINMAN
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依托单位:
QUINOENZYMES--BIOGENESIS STRUCTURE AND FUNCTION
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批准号:2331968
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项目类别:
-
资助金额:$24.29万
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财政年份:1988
-
负责人:JUDITH P KLINMAN
-
依托单位:
PROBES OF STRUCTURE & MECHANISM IN COPPER AMINE OXIDASES
-
批准号:2179737
-
项目类别:
-
资助金额:$19.41万
-
财政年份:1988
-
负责人:JUDITH P KLINMAN
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依托单位:
Protein- and Peptide-Derived Cofactors
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批准号:7009988
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项目类别:
-
资助金额:$44.76万
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财政年份:1988
-
负责人:JUDITH P KLINMAN
-
依托单位:
QUINOENZYMES: BIOGENESIS, STRUCTURE AND FUNCTION
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批准号:6351183
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项目类别:
-
资助金额:$36.08万
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财政年份:1988
-
负责人:JUDITH P KLINMAN
-
依托单位:
QUINOENZYMES: BIOGENESIS, STRUCTURE AND FUNCTION
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批准号:6628806
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项目类别:
-
资助金额:$33.77万
-
财政年份:1988
-
负责人:JUDITH P KLINMAN
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依托单位:
Protein and Peptide Derived Cofactors
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批准号:8638969
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项目类别:
-
资助金额:$38.34万
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财政年份:1988
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负责人:JUDITH P KLINMAN
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依托单位:
Protein and Peptide-Derived Redox Cofactors: Biogenesis and Function
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批准号:8066410
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项目类别:
-
资助金额:$47.02万
-
财政年份:1988
-
负责人:JUDITH P KLINMAN
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依托单位:
海外基金