Bridging Project 3: Glutathione Transferase (GST) Superfamily
Bridging Project 3: Glutathione Transferase (GST) Superfamily
批准号:
7980209
负责人:
JOHN A GERLT
金额:
$30.12万
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:
2010-05-20 至 2015-04-30
关键词:
Academic Medical CentersAerobicBacteriaBindingBiological ProcessBiologyC-terminalClassificationComputer SimulationConsensusCrystallizationDisulfidesDockingDrug Metabolic DetoxicationEpoxy CompoundsEscherichia coliEukaryotaEvaluationFamily memberGenetic ScreeningGenomeGlutathione S-TransferaseHomeostasisHomologous GeneHydrogen PeroxideHydrolysisIonsKnowledgeLibrariesLigandsMammalsMembraneMicrobiologyMissionN-terminalOrangesOrganismOxidation-ReductionPlayProductionProteinsReactionRoleScanningStructureSulfhydryl CompoundsThioredoxinTo specifyTranscriptional RegulationTransferaseTranslationsXenobioticsaryl halidedetoxicationdimerfunctional groupgenome sequencinghigh throughput screeningknockout genemembermicroorganismprotein foldingprotein functionprotein protein interactionprotein structureselenatevirtual
中文摘要
GST超家族是一大类蛋白质,其成员由两个结构域组成,N端结合GSH的硫氧还蛋白样结构域(橙色)和C端全a螺旋结构域(蓝色),如来自的GST蛋白的结构所示。Coli在右图[1,2]中。这些蛋白质存在于大多数有氧运动中
有机体。
GST是45年前在哺乳动物身上发现的[3]。在最初的30年里,它们在生物学上的作用被认为完全在于通过催化GSH加成到亲电官能团来解毒内源和外源化合物,如方程所示。1.这些反应包括
亲电性,如环氧化物、烯酮、烷基和芳基卤化物。GSTs的催化多样性还包括异构化反应、水解反应和氧化还原反应。
含有有机过氧化氢、二硫化物,或许还有亚硒化物和亚硒酸盐。这些蛋白质的功能多样性超过了它们的催化杂乱程度。在细菌和真核生物中,这些蛋白质参与解毒反应、分解代谢、转录和翻译的调节、离子的跨膜电导以及(我们几乎可以肯定的)硫醇动态平衡和蛋白质折叠。
编码的大约4,400种蛋白质中有9种。Coli基因组编码GST同源物[2,4]。
在大肠杆菌中发现的GST同源物的共识残基显示在上面结构中的空间填充表示中,以强调GST家族成员中高度保守的残基主要参与折叠的结构稳定性,而不是蛋白质的功能。硫氧还蛋白类结构域的主要作用是结合GSH或相关的配体,而α-螺旋结构域则倾向于指定蛋白质功能的更微妙的方面。这些蛋白质通常是二聚体。
英文摘要
The GST superfamily is a large group of proteins, the members of which are composed of two domains, an N-terminal thioredoxin-like domain (orange) that binds GSH, and a C-terminal all a-helical domain (blue), as illustrated by the structure of the GST protein from ¿. coli in the figure to the right [1, 2). These proteins are found in most aerobic
organisms.
The GSTs were discovered in mammals over forty-five years ago [3]. For the first thirty years, their role in biology was thought to lie exclusively in the detoxification of endogenous and xenobiotic compounds by catalyzing the addition of GSH to electrophilic functional groups, as illustrated in Eq. 1. These reactions include
electrophiles such as epoxides, enones and alkyl and aryl halides The catalytic diversity of GSTs also includes isomerization reactions, hydrolysis, and redox reactions
with organic hydroperoxides, disulfides and, perhaps, selenides and selenates. The functional diversity of these proteins exceeds their catalytic promiscuity. In bacteria and eukaryotes, the proteins are involved in detoxication reactions, catabollsm, the regulation of transcription and translation, the conductance of ions across membranes, and (we are almost sure) thiol homeostasis and protein folding.
Nine of the approximately 4,400 proteins encoded by the ¿. coli genome encode GST homologs [2, 4).
The consensus residues for the GST homologs found in E. coli are shown in space-filling representation in the structure above to highlight the fact that the highly conserved residues in GST family members are principally involved in the structural stability of the fold rather than the function of the protein. The principal role of the thioredoxin-like domain is to bind GSH or related ligands while the a-helical domain tends to specify more subtle aspects ofthe protein function. The proteins are typically dimers.
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Web-Based Resource for Genomic Enzymology Tools
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批准号:10548888
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项目类别:
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资助金额:$56.12万
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财政年份:2022
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负责人:JOHN A GERLT
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依托单位:
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批准号:9918932
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财政年份:2016
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负责人:JOHN A GERLT
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依托单位:
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批准号:9073786
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项目类别:
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资助金额:$42.29万
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财政年份:2016
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负责人:JOHN A GERLT
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依托单位:
Novel Strategies for the Discovery of Microbial Metabolic Pathways
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批准号:9297333
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项目类别:
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资助金额:$232.88万
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财政年份:2016
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负责人:JOHN A GERLT
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依托单位:
Novel Strategies for the Discovery of Microbial Metabolic Pathways
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批准号:9557783
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项目类别:
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资助金额:$11.68万
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财政年份:2016
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负责人:JOHN A GERLT
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依托单位:
GENOMIC ENZYMOLOGY: THE ENOLASE SUPERFAMILY AND OMPDC SUPRAFAMILY
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批准号:8363583
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项目类别:
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资助金额:$1.68万
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财政年份:2011
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负责人:JOHN A GERLT
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依托单位:
DECIPHERING ENZYME SPECIFICITY
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批准号:8363605
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项目类别:
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资助金额:$1.68万
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财政年份:2011
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负责人:JOHN A GERLT
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依托单位:
COLLABORATIVE CENTER FOR AN ENZYME FUNCTION INITIATIVE
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批准号:7901811
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项目类别:
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资助金额:$702.3万
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财政年份:2010
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负责人:JOHN A GERLT
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依托单位:
Core A: Administrative Core
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批准号:7980192
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项目类别:
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资助金额:$49.22万
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财政年份:2010
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负责人:JOHN A GERLT
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依托单位:
Core F: Structure
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批准号:7980201
-
项目类别:
-
资助金额:$76.19万
-
财政年份:2010
-
负责人:JOHN A GERLT
-
依托单位:
GENOMIC ENZYMOLOGY: THE ENOLASE SUPERFAMILY AND OMPDC SUPRAFAMILY
-
批准号:8170502
-
项目类别:
-
资助金额:$1.79万
-
财政年份:2010
-
负责人:JOHN A GERLT
-
依托单位:
Core G: Computation
-
批准号:7980202
-
项目类别:
-
资助金额:$103.88万
-
财政年份:2010
-
负责人:JOHN A GERLT
-
依托单位:
Core D: Superfamily/Genome
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批准号:7980199
-
项目类别:
-
资助金额:$35.29万
-
财政年份:2010
-
负责人:JOHN A GERLT
-
依托单位:
DECIPHERING ENZYME SPECIFICITY
-
批准号:8170532
-
项目类别:
-
资助金额:$1.79万
-
财政年份:2010
-
负责人:JOHN A GERLT
-
依托单位:
COLLABORATIVE CENTER FOR AN ENZYME FUNCTION INITIATIVE
-
批准号:8074489
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项目类别:
-
资助金额:$647.68万
-
财政年份:2010
-
负责人:JOHN A GERLT
-
依托单位:
COLLABORATIVE CENTER FOR AN ENZYME FUNCTION INITIATIVE
-
批准号:8489131
-
项目类别:
-
资助金额:$625.01万
-
财政年份:2010
-
负责人:JOHN A GERLT
-
依托单位:
Bridging Project 4: Haloacid Dehalogenase (HAD) Superfamily
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批准号:7980210
-
项目类别:
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资助金额:$40.76万
-
财政年份:2010
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负责人:JOHN A GERLT
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依托单位:
Core B/C: Data & Dissemination
-
批准号:7980195
-
项目类别:
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资助金额:$39.36万
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财政年份:2010
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负责人:JOHN A GERLT
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依托单位:
Core E: Protein
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批准号:7980200
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项目类别:
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资助金额:$167.1万
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财政年份:2010
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负责人:JOHN A GERLT
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依托单位:
COLLABORATIVE CENTER FOR AN ENZYME FUNCTION INITIATIVE
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批准号:8665973
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项目类别:
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资助金额:$582.91万
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财政年份:2010
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负责人:JOHN A GERLT
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依托单位:
海外基金