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Full-Text Articles in Biochemistry
Kinase-Catalyzed Labeling To Identify Kinase-Substrate Pairs Using Γ-Phosphate Modified Atp Analogs, Rachel Beltman
Kinase-Catalyzed Labeling To Identify Kinase-Substrate Pairs Using Γ-Phosphate Modified Atp Analogs, Rachel Beltman
Wayne State University Dissertations
Post-translational modifications (PTMs) are responsible for a variety of cellular processes. One such PTM is protein phosphorylation, which is catalyzed by kinases. Kinase enzymes play important roles in cellular signaling pathways, but dysregulation of kinase-mediated events results in the formation of diseases, which make kinases favorable drug targets. To uncover the role kinases play in the development of diseases, kinase-mediated cellular events need to be better understood. The current gap in the field is the lack of tools available to identify the kinase that is responsible for specific phosphorylation events within the cell. To improve the gap in the field, …
Identification Of Fluoxetine-Sert Interactions And Apo-Sert Studies Via Crosslinking Mass Spectrometry, Elizabeth Castellano
Identification Of Fluoxetine-Sert Interactions And Apo-Sert Studies Via Crosslinking Mass Spectrometry, Elizabeth Castellano
Electronic Theses and Dissertations
The serotonin transporter (SERT) is a member of the neurotransmitter sodium symporter family of transporters. SERT controls the magnitude and duration of serotonergic neurotransmission by facilitating the reuptake of serotonin back into the pre-synaptic neuron and is thus a target for antidepressants. Selective serotonin re-uptake inhibitors (SSRIs) such as fluoxetine, are commonly prescribed to treat depression. SSRIs act by blocking reuptake and prolonging serotonin signaling. However, significant problems regarding selectivity and mechanisms of action of these drugs remain unresolved. The structures of SERT and related transporters have been determined and serve as useful structural models. However, they are typically mutated …
Development Of Gamma-Modified Atp Analogs To Study Kinase-Catalyzed Phosphorylations, Ahmed Eid Fouda
Development Of Gamma-Modified Atp Analogs To Study Kinase-Catalyzed Phosphorylations, Ahmed Eid Fouda
Wayne State University Dissertations
Kinase-catalyzed protein phosphorylation is one of the most important post-translational modifications that controls cascades of biochemical reactions. Irregularities in phosphorylation result in many diseases, such as diabetes mellitus, Parkinsons, and cancer. The development of new methods to monitor kinase-catalyzed phosphorylation is needed to decipher details of normal and diseased cell signaling. The Pflum lab recently developed several -modified ATP analogs to study kinase catalyzed phosphorylation reactions. The -modified ATP analogs have different tags, such as biotin for substrate labeling or aryl-azide for kinase substrates identification. Unfortunately, use of -modified ATP analogs was limited to in vitro studies due to the …
Towards Structural Determination Of Human Α1-Glycine Receptor Allostery, Rathna Jyothi Veeramachaneni
Towards Structural Determination Of Human Α1-Glycine Receptor Allostery, Rathna Jyothi Veeramachaneni
Electronic Theses and Dissertations
Recent advances in technology have led to the determination of numerous notable structures of membrane proteins. While they provide valuable information about the structure of membrane proteins these studies often provide static images with potentially limited dynamics, and structural determination often requires truncation of flexible regions, and often utilizes bacterial homologs given the need for stable, heterologous overexpression. In order to better understand allostery at a molecular level, state-dependent crosslinking studies coupled with multidimensional mass spectrometry (MS) were conducted on glycine receptor (GlyR) stabilized in different allosteric states. Predominant allosteric states were stabilized using wild type or mutated receptor in …
Synthesis And Application Of Atp Analogs For Phosphorylation-Dependent Kinase-Substrate Crosslinking, Satish Kumar Garre Venkata Raghavendra
Synthesis And Application Of Atp Analogs For Phosphorylation-Dependent Kinase-Substrate Crosslinking, Satish Kumar Garre Venkata Raghavendra
Wayne State University Dissertations
Phosphorylation is an important post-translational modification that plays a key role in a variety of signaling cascades and cellular functions. Kinases phosphorylate protein substrates in a highly regulated manner and are promiscuous. Understanding kinase-substrate specificity has been challenging and there is a need for new chemical tools. To this end we developed -phosphate modified ATP photocrosslinking analogs ATP-ArN3 and ATP-BP, that crosslink substrate and kinase in a phosphorylation dependent manner. We have successfully demonstrated that ATP-ArN3 and ATP-BP can be used with natural kinase and substrates using cell lysates in vitro. We used our approach to identify novel kinases of …