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Structural and Functional Characterization of Strigolactone Perception and Hydrolysis, the Discovery of Inhibitors for Striga, and Insights into the Evolution of Parasitic Receptors =Caracterizacion Estructural y Funcional de la Percepcion e Hidrolisis de Estrigolactonas; el Descubrimiento de Inhibidores de Striga y la Evolucion de sus Receptores Parasiticos.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Structural and Functional Characterization of Strigolactone Perception and Hydrolysis, the Discovery of Inhibitors for Striga, and Insights into the Evolution of Parasitic Receptors =
其他題名:	Caracterizacion Estructural y Funcional de la Percepcion e Hidrolisis de Estrigolactonas; el Descubrimiento de Inhibidores de Striga y la Evolucion de sus Receptores Parasiticos.
作者:	Arellano Saab, Amir Alam.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, 2022
面頁冊數:	220 p.
附註:	Source: Dissertations Abstracts International, Volume: 84-01, Section: B.
附註:	Includes supplementary digital materials.
附註:	Advisor: McCourt, Peter.
Contained By:	Dissertations Abstracts International84-01B.
標題:	Biochemistry.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29065228
ISBN:	9798835526437

Structural and Functional Characterization of Strigolactone Perception and Hydrolysis, the Discovery of Inhibitors for Striga, and Insights into the Evolution of Parasitic Receptors =Caracterizacion Estructural y Funcional de la Percepcion e Hidrolisis de Estrigolactonas; el Descubrimiento de Inhibidores de Striga y la Evolucion de sus Receptores Parasiticos.
Arellano Saab, Amir Alam.

Structural and Functional Characterization of Strigolactone Perception and Hydrolysis, the Discovery of Inhibitors for Striga, and Insights into the Evolution of Parasitic Receptors =Caracterizacion Estructural y Funcional de la Percepcion e Hidrolisis de Estrigolactonas; el Descubrimiento de Inhibidores de Striga y la Evolucion de sus Receptores Parasiticos. - Ann Arbor : ProQuest Dissertations & Theses, 2022 - 220 p.

Source: Dissertations Abstracts International, Volume: 84-01, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2022.

This item must not be sold to any third party vendors.

Striga spp. is the most destructive food crop parasite in the developing world. It invades its hosts by perceiving host-derived hormones called strigolactones (SLs). The receptors in charge of sensing SLs belong to a group of α/β hydrolases that not only recognize SLs but also hydrolyze them. To understand this perception-signalling mechanism at a molecular level, and prevent the parasite from invading a potential host, I generated structural information from its SL receptors and used this information to dissect function. Using this structural information in combination with in silico, in vitro and in vivo experiments, I designed a hybrid drug-discovery approach to find and optimize a group of antagonist molecules that can specifically bind and inactivate the parasitic receptors. Subsequently, I discovered dormirazine, a potent antagonist that reduces parasitic germination by 90%. Additionally, this compound helped us reveal parallels between the germination of parasitic and non-parasitic organisms. Also, I leveraged the first structure of a parasitic SL receptor bound to its ligand, in combination with targeted mutagenesis, to characterize the structural mechanisms that drive SL perception and hydrolysis, and typified the conformational changes required to promote protein signalling. I described the existence of a tunnel that could drive the release of SL hydrolysis by-products which possibly contribute to biological function using a push-over mechanism. Lastly, using a series of molecular dynamics simulations and biochemical experiments, I defined the importance of protein flexibility for substrate recognition and its influence on the evolution of parasitism. Collectively, my thesis projects apply a wide range of structural biochemistry techniques to dissect the molecular mechanisms behind the pernicious Striga and propose targeted solutions to control it with the ultimate goal of helping populations in need.

ISBN: 9798835526437Subjects--Topical Terms:

188609
Biochemistry.
Subjects--Index Terms:

Antagonist

Structural and Functional Characterization of Strigolactone Perception and Hydrolysis, the Discovery of Inhibitors for Striga, and Insights into the Evolution of Parasitic Receptors =Caracterizacion Estructural y Funcional de la Percepcion e Hidrolisis de Estrigolactonas; el Descubrimiento de Inhibidores de Striga y la Evolucion de sus Receptores Parasiticos.
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245 1 0 $a Structural and Functional Characterization of Strigolactone Perception and Hydrolysis, the Discovery of Inhibitors for Striga, and Insights into the Evolution of Parasitic Receptors = $b Caracterizacion Estructural y Funcional de la Percepcion e Hidrolisis de Estrigolactonas; el Descubrimiento de Inhibidores de Striga y la Evolucion de sus Receptores Parasiticos.
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500 $a Source: Dissertations Abstracts International, Volume: 84-01, Section: B.
500 $a Includes supplementary digital materials.
500 $a Advisor: McCourt, Peter.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2022.
506 $a This item must not be sold to any third party vendors.
520 $a Striga spp. is the most destructive food crop parasite in the developing world. It invades its hosts by perceiving host-derived hormones called strigolactones (SLs). The receptors in charge of sensing SLs belong to a group of α/β hydrolases that not only recognize SLs but also hydrolyze them. To understand this perception-signalling mechanism at a molecular level, and prevent the parasite from invading a potential host, I generated structural information from its SL receptors and used this information to dissect function. Using this structural information in combination with in silico, in vitro and in vivo experiments, I designed a hybrid drug-discovery approach to find and optimize a group of antagonist molecules that can specifically bind and inactivate the parasitic receptors. Subsequently, I discovered dormirazine, a potent antagonist that reduces parasitic germination by 90%. Additionally, this compound helped us reveal parallels between the germination of parasitic and non-parasitic organisms. Also, I leveraged the first structure of a parasitic SL receptor bound to its ligand, in combination with targeted mutagenesis, to characterize the structural mechanisms that drive SL perception and hydrolysis, and typified the conformational changes required to promote protein signalling. I described the existence of a tunnel that could drive the release of SL hydrolysis by-products which possibly contribute to biological function using a push-over mechanism. Lastly, using a series of molecular dynamics simulations and biochemical experiments, I defined the importance of protein flexibility for substrate recognition and its influence on the evolution of parasitism. Collectively, my thesis projects apply a wide range of structural biochemistry techniques to dissect the molecular mechanisms behind the pernicious Striga and propose targeted solutions to control it with the ultimate goal of helping populations in need.
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650 4 $a Genetics. $3 189015
650 4 $a Plant sciences. $3 915551
653 $a Antagonist
653 $a Drug discovery
653 $a Molecular dynamics
653 $a Protein engineering
653 $a Striga
653 $a Structural biology
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710 2 $a University of Toronto (Canada). $b Cell and Systems Biology. $3 942387
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