FUNCTIONAL PROMISCUITY IN O-SUCCINYLBENZOATE SYNTHASE
FUNCTIONAL PROMISCUITY IN O-SUCCINYLBENZOATE SYNTHASE
批准号:
8170521
负责人:
PATRICIA CLEMENT BABBITT
金额:
$0.7万
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-07-01 至 2011-06-30
关键词:
AcidsAffectCatalysisChimera organismComputer Retrieval of Information on Scientific Projects DatabaseComputer softwareDatabasesEnzymesEvolutionFamilyFundingGCG geneGoalsGrantInstitutionMediatingMutagenesisMutationPhylogenetic AnalysisReactionResearchResearch PersonnelResourcesSourceStructureUnited States National Institutes of Healthbasedesignenolasememberprotein structureracemization
中文摘要
这个子项目是许多研究子项目中利用
资源由NIH/NCRR资助的中心拨款提供。子项目和
调查员(PI)可能从NIH的另一个来源获得了主要资金,
并因此可以在其他清晰的条目中表示。列出的机构是
该中心不一定是调查人员的机构。
本项目的目标是确定烯醇化酶超家族成员o-琥珀酰基苯甲酸合成酶(OSBS)催化杂乱的结构基础。OSBS家族的成员只有15%的同源性,家族中唯一保守的残基也在烯醇化酶超家族的其他成员中保守,这些成员催化不同的反应。这表明,尽管OSBS功能在进化过程中一直保持不变,但决定这一功能的残基和结构已经分化进化,不是保守的。我们正在通过结构比较来确定OSBS催化的结构基础,以合理设计预测会影响OSBS活性的突变。此外,OSBS家族的一个分支的许多成员还催化第二个反应,N-琥珀酰氨基酸外消旋(NSAR)。我们正在进行结构、系统发育和突变研究,以确定OSBS家族的一些成员如何催化NSAR反应,而其他成员则不能。该项目将利用几个RBVI资源,包括Chimera、结构功能链接数据库,以及通过RBVI提供的软件,如GCG和Mr Bayes。比较OSBS家族的结构、功能和进化将有助于我们理解蛋白质的功能可塑性以及结构如何调节功能。
英文摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
The goal of this project is to determine the structural basis of catalytic promiscuity in the enzyme o-Succinylbenzoate synthase (OSBS), a member of the enolase superfamily. Members of the OSBS family can share as little as 15% identity, and the only conserved residues in the family are also conserved in other members of the enolase superfamily which catalyze different reactions. This suggests that although OSBS function has been maintained during the course of evolution, the residues and structures that determine this function have evolved divergently and are not conserved. We are determining the structural basis for OSBS catalysis by using structural comparisons to rationally design mutations that are predicted to affect OSBS activity. In addition, many members of one branch of the OSBS family catalyze a second reaction, N-succinylamino acid racemization (NSAR). We are performing structural, phylogenetic, and mutagenesis studies to determine how some members of the OSBS family can catalyze the NSAR reaction while others cannot. This project will utilize several RBVI resources, including Chimera, the Structure Function Linkage Database, and software available through RBVI such as GCG and MrBayes. Comparing structures, function and evolution of the OSBS family will add to our understanding about the functional plasticity of proteins and how structure mediates function.
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THE STRUCTURE-FUNCTION LINKAGE DATABASE
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批准号:8363588
-
项目类别:
-
资助金额:$2.79万
-
财政年份:2011
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
LAYING THE FOUNDATIONS FOR GENOMIC ENZYMOLOGY
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批准号:8363593
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项目类别:
-
资助金额:$1.68万
-
财政年份:2011
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负责人:PATRICIA CLEMENT BABBITT
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依托单位:
ACTIVE SITE SIGNATURES FOR SFLD: ENOLASE SUPERFAMILY
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批准号:8363627
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项目类别:
-
资助金额:$1.68万
-
财政年份:2011
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
ACTIVE SITE SIGNATURES FOR AUTOMATIC UPDATES OF SFLD SUPERFAMILIES
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批准号:8363621
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项目类别:
-
资助金额:$1.68万
-
财政年份:2011
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
ENZYME ACTIVE SITE TEMPLATES
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批准号:8363587
-
项目类别:
-
资助金额:$1.68万
-
财政年份:2011
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
A COMPUTATIONAL ATLAS OF THE T BRUCEI DEGRADOME AS A GUIDE TO DRUG DISCOVERY
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批准号:8363620
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项目类别:
-
资助金额:$1.68万
-
财政年份:2011
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
ACTIVE SITE SIGNATURES FOR SFLD: KINASE SUPERFAMILY
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批准号:8363628
-
项目类别:
-
资助金额:$1.68万
-
财政年份:2011
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
ENZYME FUNCTION INITIAVE
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批准号:8363638
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项目类别:
-
资助金额:$1.68万
-
财政年份:2011
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
ENZYME ACTIVE SITE TEMPLATES
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批准号:8170507
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项目类别:
-
资助金额:$1.79万
-
财政年份:2010
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
ACTIVE SITE SIGNATURES FOR SFLD: ENOLASE SUPERFAMILY
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批准号:8170567
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项目类别:
-
资助金额:$1.79万
-
财政年份:2010
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
ROADMAP FOR DRUG DISCOVERY IN SMALL MOLECULE METABOLISM
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批准号:8170555
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项目类别:
-
资助金额:$1.79万
-
财政年份:2010
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
IGTC (PGA) TRAINING AND OUTREACH
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批准号:8170549
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项目类别:
-
资助金额:$1.89万
-
财政年份:2010
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
LAYING THE FOUNDATIONS FOR GENOMIC ENZYMOLOGY
-
批准号:8170514
-
项目类别:
-
资助金额:$1.79万
-
财政年份:2010
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
THE STRUCTURE-FUNCTION LINKAGE DATABASE
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批准号:8170509
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项目类别:
-
资助金额:$2.66万
-
财政年份:2010
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
ACTIVE SITE SIGNATURES FOR AUTOMATIC UPDATES OF SFLD SUPERFAMILIES
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批准号:8170559
-
项目类别:
-
资助金额:$1.79万
-
财政年份:2010
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
ACTIVE SITE SIGNATURES FOR SFLD: KINASE SUPERFAMILY
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批准号:8170568
-
项目类别:
-
资助金额:$1.79万
-
财政年份:2010
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
CYTOSCAPE AND BIOLOGICAL CONTEXT OUTREACH AND TRAINING
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批准号:8170550
-
项目类别:
-
资助金额:$1.89万
-
财政年份:2010
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
A COMPUTATIONAL ATLAS OF THE T BRUCEI DEGRADOME AS A GUIDE TO DRUG DISCOVERY
-
批准号:8170558
-
项目类别:
-
资助金额:$1.79万
-
财政年份:2010
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
ACTIVE SITE SIGNATURES FOR AUTOMATIC UPDATES OF SFLD SUPERFAMILIES
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批准号:7955530
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项目类别:
-
资助金额:$2.38万
-
财政年份:2009
-
负责人:PATRICIA CLEMENT BABBITT
-
依托单位:
THE STRUCTURE-FUNCTION LINKAGE DATABASE
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批准号:7955474
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项目类别:
-
资助金额:$5.03万
-
财政年份:2009
-
负责人:PATRICIA CLEMENT BABBITT
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依托单位:
海外基金