Structure and function of glutamate transporters

The work presented in the following chapters primarily involves determining specific structural and functional features involved with glutamate transport by the excitatory amino acid transporters (EAAT1-5). This research derives from a study of X-ray crystal structures of an homologous archaeal transporter. Broadly, using computational methods to probe EAAT homology models born from the archaeal structures, we introduce/describe novel Na+ and K+ coordination sites and present a model for sequential cation and substrate binding and unbinding during the transport cycle. A secondary focus of this dissertation was computational modeling of two other proteins: the HIV gp120 envelope protein (gp120) and NAD(P)H:Quinone Oxidoreductase 1 (NQO1). The study of gp120 involved a statistical analysis of substitutions that occur during early infection of clade A HIV, showing that during early infection substitutions are non-random and co-locate in regions associated with receptor binding. The computational component of the study involving NQO1 used computational molecular docking of two lavendamycin analogues into the NQO1 active site. Here we showed that relative scores of docked poses of the analogues were consistent with in vitro evaluations. All the studies presented in this dissertation were collaborative efforts that linked in silico work with in vitro analysis.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Grantor dc:publisher

University of Montana

Year

2010

Author dc:creator

• Holley, David Charles

• EAAT
• glutamate transporter
• transporter structure

Repository record dc:identifier

https://scholarworks.umt.edu/etd/922

OAI identifier oai:identifier

oai:scholarworks.umt.edu:etd-1941