Relationship between function and 3D-structure of interferon inducible GTPases

  • The thesis work covers structural investigation of IIGP1, structural basis of GTP cleavage mechanism of hGBP1 and the biochemical characterization of hGBP2. The structure of IIGP1 was refined as nucleotide-free, and in complex with GDP-\(Mg^{2+}\) and GppNHp-\(Mg^{2+}\) at a resolution of 2.3Å, 2.0Å and 2.7Å, respectively. IIGP1 consists of a G domain and a purely \(\alpha\)-helical domain. Comparison of the three structures enables to put insight into the reaction mechanism. hGBP1 hydrolyses GTP to GDP and GMP after successive cleavage of two terminal phosphates and shows GTP dependent dimerization. The crystal structures of the G domain have been solved as nucleotide-free and incomplex with GMP, GMP \(\bullet\) \(AlF_{4-}-Mg^{2+}\) and GppNHp-\(Mg^{2+}\) at a resolution of 3.1Å, 2.9Å, 2.2Å and 2.7Å, respectively. These multiple structures enable to explain the cleavage reactions of hGBP1. hGBP2 shares 82% sequence identity with hGBP1. The biochemical studies on hGBP2 show that the two proteins differ in their biochemical properties.

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Metadaten
Author:Agnidipta GhoshGND
URN:urn:nbn:de:hbz:294-10904
Referee:Alfred WittinghoferGND, William S. SheldrickGND
Document Type:Doctoral Thesis
Language:English
Date of Publication (online):2004/07/30
Date of first Publication:2004/07/30
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Granting Institution:Ruhr-Universität Bochum, Fakultät für Chemie und Biochemie
Date of final exam:2004/02/09
Creating Corporation:Fakultät für Chemie und Biochemie
GND-Keyword:GTP-bindende Proteine; Interferon; Kristallographie; Dimer-Konfiguration; Immunologie
Institutes/Facilities:Max-Planck-Institut für molekulare Physiologie, Dortmund, Abteilung "Strukturelle Biologie"
Dewey Decimal Classification:Naturwissenschaften und Mathematik / Chemie, Kristallographie, Mineralogie
faculties:Fakultät für Chemie und Biochemie
Licence (German):License LogoKeine Creative Commons Lizenz - es gelten der Veröffentlichungsvertrag und das deutsche Urheberrecht