velikost textu

Characterization of recombinant human serine racemase

Upozornění: Informace získané z popisných dat či souborů uložených v Repozitáři závěrečných prací nemohou být použity k výdělečným účelům nebo vydávány za studijní, vědeckou nebo jinou tvůrčí činnost jiné osoby než autora.
Název:
Characterization of recombinant human serine racemase
Název v češtině:
Charakterizace rekombinantní lidské serinracemasy
Typ:
Disertační práce
Autor:
Hillary Elizabeth Hoffman, Ph.D.
Školitel:
doc. RNDr. Jan Konvalinka, CSc.
Oponenti:
prof. Ing. Vladimír Křen, DrSc.
doc. RNDr. Noemi Čeřovská, CSc.
Id práce:
83669
Fakulta:
Přírodovědecká fakulta (PřF)
Pracoviště:
Katedra biochemie (31-250)
Program studia:
Biochemie (P1406)
Obor studia:
-
Přidělovaný titul:
Ph.D.
Datum obhajoby:
11. 2. 2010
Výsledek obhajoby:
Prospěl/a
Informace o neveřejnosti:
Příloha práce byla vyloučena ze zveřejnění.
Jazyk práce:
Angličtina
Abstrakt:
Brief Abstract The pyridoxal-5’-phosphate-dependent enzyme serine racemase (SR) is responsible for the biosynthesis of D-serine in the mammalian central nervous system. D-serine acts as a neurotransmitter and coagonist, together with L-glutamate, of ionotropic N-methyl-D-aspartate receptors (NMDARs). Excitotoxic D-serine levels have been implicated in neuropathologies including Alzheimer’s disease and amyotrophic lateral sclerosis. SR inhibitors offer a novel and potentially highly specific approach for attenuation of NMDAR-mediated glutamate excitotoxicity and for further study of the pathway. Many of the SR inhibitors described to date are small, naturally occurring compounds, and novel structures capable of influencing SR’s activity are highly sought after. Moreover, structural information about this enigmatic enzyme is lacking, and suitable animal models need to be identified for inhibitor studies. This thesis presents the first published biochemical comparison of mouse and human SR orthologs, validating, at least in part, the use of mouse models in SR research. Additionally, hydroxamic acids are introduced as a novel class of SR inhibitors. While the experimentally determined structure of a mammalian SR remains elusive, random and site-directed mutagenesis experiments in combination with multiple sequence alignment offer insight into structure- function relationships within the enzyme. 6
Abstract v angličtině:
Brief Abstract The pyridoxal-5’-phosphate-dependent enzyme serine racemase (SR) is responsible for the biosynthesis of D-serine in the mammalian central nervous system. D-serine acts as a neurotransmitter and coagonist, together with L-glutamate, of ionotropic N-methyl-D-aspartate receptors (NMDARs). Excitotoxic D-serine levels have been implicated in neuropathologies including Alzheimer’s disease and amyotrophic lateral sclerosis. SR inhibitors offer a novel and potentially highly specific approach for attenuation of NMDAR-mediated glutamate excitotoxicity and for further study of the pathway. Many of the SR inhibitors described to date are small, naturally occurring compounds, and novel structures capable of influencing SR’s activity are highly sought after. Moreover, structural information about this enigmatic enzyme is lacking, and suitable animal models need to be identified for inhibitor studies. This thesis presents the first published biochemical comparison of mouse and human SR orthologs, validating, at least in part, the use of mouse models in SR research. Additionally, hydroxamic acids are introduced as a novel class of SR inhibitors. While the experimentally determined structure of a mammalian SR remains elusive, random and site-directed mutagenesis experiments in combination with multiple sequence alignment offer insight into structure- function relationships within the enzyme. 6
Dokumenty
Stáhnout Dokument Autor Typ Velikost
Stáhnout Text práce Hillary Elizabeth Hoffman, Ph.D. 1.33 MB
Stáhnout Abstrakt v českém jazyce Hillary Elizabeth Hoffman, Ph.D. 23 kB
Stáhnout Abstrakt anglicky Hillary Elizabeth Hoffman, Ph.D. 23 kB
Stáhnout Posudek oponenta prof. Ing. Vladimír Křen, DrSc. 83 kB
Stáhnout Posudek oponenta doc. RNDr. Noemi Čeřovská, CSc. 1.18 MB
Stáhnout Záznam o průběhu obhajoby 649 kB