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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.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Structural and Functional Characterization of Strigolactone Perception and Hydrolysis, the Discovery of Inhibitors for Striga, and Insights into the Evolution of Parasitic Receptors =/
Reminder of title:	Caracterizacion Estructural y Funcional de la Percepcion e Hidrolisis de Estrigolactonas; el Descubrimiento de Inhibidores de Striga y la Evolucion de sus Receptores Parasiticos.
remainder title:	Caracterizacion Estructural y Funcional de la Percepcion e Hidrolisis de Estrigolactonas; el Descubrimiento de Inhibidores de Striga y la Evolucion de sus Receptores Parasiticos.
Author:	Arellano Saab, Amir Alam.
Description:	1 online resource (220 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 84-01, Section: B.
Contained By:	Dissertations Abstracts International84-01B.
Subject:	Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29065228click for full text (PQDT)
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.Caracterizacion Estructural y Funcional de la Percepcion e Hidrolisis de Estrigolactonas; el Descubrimiento de Inhibidores de Striga y la Evolucion de sus Receptores Parasiticos. - 1 online resource (220 pages)

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

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

Includes bibliographical references

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.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798835526437Subjects--Topical Terms:

518028
Biochemistry.
Subjects--Index Terms:

AntagonistIndex Terms--Genre/Form:

542853
Electronic books.

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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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.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2023
538 $a Mode of access: World Wide Web
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650 4 $a Genetics. $3 530508
650 4 $a Plant sciences. $3 3173832
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