Hemostasis and Thrombosis: Chemistry, Biology and Physiology
止血和血栓形成:化学、生物学和生理学
基本信息
- 批准号:9982398
- 负责人:
- 金额:$ 206.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAreaBiochemicalBiochemistryBiologicalBiological ProcessBiologyBlood VesselsBlood coagulationChemistryCoagulation ProcessComplexDeuteriumDiseaseEnsureEnzymesFactor VFactor VaFoundationsGoalsHemophilia AHemorrhageHemostatic AgentsHemostatic functionHydrogenIndividualKineticsKnowledgeLeadLifeMembraneMembrane ProteinsMolecularMolecular BiologyMultienzyme ComplexesMyocardial InfarctionParticipantPeptide HydrolasesPhysiologyPlayProteinsRNAReactionReagentRecombinantsRecordsRegulation of ProteolysisResearchResearch PersonnelRoentgen RaysRoleSeriesSerine ProteaseSpecificityStrokeStructureSubstrate InteractionSubstrate SpecificityTestingTherapeuticThrombosisThrombusTrypsinVariantWestern WorldX-Ray Crystallographyaptamerbasebiophysical analysisbiophysical techniquescancer procoagulantcofactorenzyme substratehuman diseasehuman morbidityhuman mortalityinsightinterdisciplinary approachinterestmouse modelnovel strategiesnovel therapeuticsprogramsprotein expressionprothrombinase complexresponsestructural biology
项目摘要
Overall Program-Abstract
Blood coagulation derives from a series of specific proteolytic activation reactions that are catalyzed with
narrow and defined specificity by trypsin-like serine proteinases. In several instances, these proteinases
function in membrane assembled enzyme complexes. Distinctive protein substrate specificities and the
modulation of enzymic function by interactions with membranes and cofactors are hallmarks of the proteolytic
reactions of blood coagulation. There are major gaps in the current understanding of the molecular bases for
these unique features that underlie the function of the hemostatic reactions. This program proposes an
integrated approach focused on the modulation of enzymic function and specificity that uniquely arises from
macromolecular interactions that underlie the action of the hemostatic enzymes. Project 1 (Krishnaswamy)
uses the prothrombinase complex as a paradigm to investigate structural and functional mechanisms deriving
from the membrane-dependent interactions between cofactor, proteinase and substrate in enzyme function.
Project 2 (Camire) will investigate molecular mechanisms at play in the conversion of factor V to the cofactor,
factor Va and the surprising new biological insights that these mechanisms reveal. Project 3 (Sullenger)
employs RNA aptamers as unique probes for the macromolecular interactions essential for coagulation
enzyme function and to show the way forward for novel approaches to either interfere with or enhance these
interactions for therapeutic gain. Project 4 (Arruda) investigates the biochemistry of intrinsic Xase with a focus
on characterizing proteinase and cofactor variants with superior function and potential for use as the next
generation of therapeutics in the treatment of hemophilia. The objectives of the four projects will be supported
by an administrative core (Core A), a core that provides support for molecular biology, protein expression and
structural biology (Core B) and a core that supports the program with mouse models of hemostasis and
thrombosis (Core C). Overall, this project applies the expertise of the individual investigators towards
addressing major unanswered questions in hemostasis and thrombosis extending from biochemical insights to
biological function and physiology. The proposed approaches will provide new insights into the chemistry and
biology of the blood coagulation reactions with implications for an understanding of normal hemostasis and
thrombosis.
整体Program-Abstract
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sriram Krishnaswamy其他文献
Sriram Krishnaswamy的其他文献
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{{ truncateString('Sriram Krishnaswamy', 18)}}的其他基金
Hemostasis and Thrombosis: Chemistry, Biology and Physiology
止血和血栓形成:化学、生物学和生理学
- 批准号:
9769852 - 财政年份:2018
- 资助金额:
$ 206.71万 - 项目类别:
Hemostasis and Thrombosis: Chemistry, Biology and Physiology
止血和血栓形成:化学、生物学和生理学
- 批准号:
10439604 - 财政年份:2018
- 资助金额:
$ 206.71万 - 项目类别:
Hemostasis and Thrombosis: Chemistry, Biology and Physiology
止血和血栓形成:化学、生物学和生理学
- 批准号:
10175000 - 财政年份:2018
- 资助金额:
$ 206.71万 - 项目类别:
Core B: Molecular Biology, Protein Expression and Structural Biology
核心 B:分子生物学、蛋白质表达和结构生物学
- 批准号:
10175002 - 财政年份:2018
- 资助金额:
$ 206.71万 - 项目类别:
Core B: Molecular Biology, Protein Expression and Structural Biology
核心 B:分子生物学、蛋白质表达和结构生物学
- 批准号:
10439607 - 财政年份:2018
- 资助金额:
$ 206.71万 - 项目类别:
2012 Hemostasis Gordon Research Conference and Gordon Research Seminar
2012止血戈登研究会议暨戈登研究研讨会
- 批准号:
8388646 - 财政年份:2012
- 资助金额:
$ 206.71万 - 项目类别:
Proteinase Allostery and the Regulation of Blood Coagulation
蛋白酶变构和凝血调节
- 批准号:
8463606 - 财政年份:2011
- 资助金额:
$ 206.71万 - 项目类别:
Proteinase Allostery and the Regulation of Blood Coagulation
蛋白酶变构和凝血调节
- 批准号:
8155012 - 财政年份:2011
- 资助金额:
$ 206.71万 - 项目类别:
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