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Direct Determination Of Multiple Ligand Interactions With The Extracellular Domain Of The Calcium Sensing Receptor, Chen Zhang, You Zhuo, Heather A. Moniz, Shuo Wang, Kelley W. Moremen, James H. Prestegard, Edward M. Brown, Jenny J. Yang
Direct Determination Of Multiple Ligand Interactions With The Extracellular Domain Of The Calcium Sensing Receptor, Chen Zhang, You Zhuo, Heather A. Moniz, Shuo Wang, Kelley W. Moremen, James H. Prestegard, Edward M. Brown, Jenny J. Yang
Chemistry Faculty Publications
Numerous in vivo functional studies have indicated that the dimeric extracellular domain (ECD) of the CaSR plays a crucial role in regulating Ca2+ homeostasis by sensing Ca2+ and L-Phe. However, direct interaction of Ca2+ and Phe with the receptor’s ECD and the resultant impact on its structure and associated conformational changes have been hampered by the large size of the ECD, its high degree of glycosylation, and the lack of biophysical methods to monitor weak interactions in solution. In the present study, we purified the glycosylated extracellular domain of CaSR (ECD) (residues 20~612), containing either complex or high mannose N-glycan …
Tuning Calcium Bindging Affinities With Related Biological Functions Of Calmodulin And Designing Protein Based Contrast Agent, Jie Jiang
Chemistry Dissertations
Calmodulin (CaM) is a ubiquitous intracellular protein that regulates biological activities of numerous enzymes and ion channels. Upon responding Ca2+ concentration change, Ca2+- dependent CaM activates the hydrolyzation of cGMP by PDE and Ca2+ releasing channel activity of ryanodine receptor. In this dissertation, a series of CaM variants were engineered to enhance Ca2+ binding affinities by increasing the number of negative charged residues in individual EF-hand. The capability of shifting the biphasic Ca2+-activation profile of RyR1 is significantly altered by changing Ca2+ binding affinity of CaM at the C-terminal. This indicates that …
Defining A Molecular Mechanism For Lead Toxicity Via Calcium-Binding Proteins, Michael Kirberger
Defining A Molecular Mechanism For Lead Toxicity Via Calcium-Binding Proteins, Michael Kirberger
Chemistry Dissertations
Essential metals like Ca2+ and Zn2+ play critical roles in biological processes through protein interactions. Conversely, non-essential metals (e.g., Gd3+ and Pb2+) also interact with proteins, often with toxic effects. Molecular metal toxicity is assumed to be due to ionic displacement, and studies have demonstrated that Pb2+ replaces Zn2+, Ca2+ and other essential metals in proteins. The focus of this work was to compare protein Ca2+ and Pb2+ -binding sites and to investigate a mechanism of Pb2+ toxicity in Ca2+-binding proteins, particularly the intracellular trigger protein …
Determining The Site Specific Metal Binding And Structural Properties Of Ef-Hand Protein Using Grafting Approach, Hsiau-Wei Lee
Determining The Site Specific Metal Binding And Structural Properties Of Ef-Hand Protein Using Grafting Approach, Hsiau-Wei Lee
Chemistry Dissertations
Calmodulin is an essential EF-hand protein with a helix-loop-helix calcium binding motif. Understanding Ca(II) dependent activation of calmodulin and other EF-hand proteins is limited by Ca(II)-induced conformational change, multiple and cooperative binding of Ca(II) ions, and interactions between the paired EF-hand motifs. The goal of this research project is to probe key determinants for calcium binding properties and pairing interactions at the site specific level using a grafting approach and high resolution NMR. An individual Ca(II) binding site of the EF-hand motifs of calmodulin was grafted into a non-calcium dependent protein, CD2, to bypass limitations associated with natural EF-hand proteins …
Rational Design Of Calcium Biosensors, April L. Ellis
Rational Design Of Calcium Biosensors, April L. Ellis
Chemistry Dissertations
Understanding the temporal and spatial changes in calcium concentration has been a difficult endeavor for many years due to the relatively small changes in calcium concentration during messenging events, the rapid changes upon physiological messenging, and the unavailability of fast, efficient, and sensitive sensors to detect calcium changes. In addition, the key factors in calcium binding have yet to be determined due to the metal-metal interactions, cooperativity, and conformational change involved in calcium binding to natural calcium-binding proteins. To overcome these obstacles and to engineer calcium sensors for in vivo studies of calcium signaling events, calcium binding sites have been …
Exploring The Role Of Calcium Ions In Biological Systems By Computational Prediction And Protein Engineering, Yubin Zhou
Exploring The Role Of Calcium Ions In Biological Systems By Computational Prediction And Protein Engineering, Yubin Zhou
Chemistry Dissertations
Ca2+, a signal for death and life, is closely involved in the regulation of numerous important cellular events. Ca2+ carries out its function through its binding to Ca2+-receptors or Ca2+-binding proteins. The EF-hand protein, with a helix-loop-helix Ca2+-binding motif, constitutes one of the largest protein families. To facilitate our understanding of the role of Ca2+ in biological systems (denoted as calciomics) using genomic information, an improved pattern search method (http://www.chemistry.gsu.edu/faculty/Yang/Calciomics.htm) for the identification of EF-hand and EF-like Ca2+-binding proteins was developed. This fast and robust method allows us to analyze putative EF-hand proteins at the genome-wide level and further visualize …