Thermodynamic Investigation into the Binding Properties of Cardiac Troponin (Human and Bovine)

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dc.contributor.advisorSpuches, Anne M.en_US
dc.contributor.authorHaulsee, Zachary Merleen_US
dc.contributor.departmentChemistryen_US
dc.date.accessioned2010-09-16T13:09:33Zen_US
dc.date.accessioned2011-05-17T14:45:30Z
dc.date.available2012-07-31T13:08:19Z
dc.date.issued2010en_US
dc.description.abstractTroponin is an integral protein in the mechanism of muscle contraction. In order to induce cardiac muscle contraction, Ca[superscript]2[superscript]+ must bind to the TnC subunit (calcium binding subunit) of troponin to begin a conformational change in the protein. The ATPase rate of myosin with actin present is cooperatively activated by Ca[superscript]2[superscript]+ and Myosin. Ca[superscript]2[superscript]+ greatly increases the rate of ATPase activity (18-fold) and decreases the concentration of actin needed for muscle contraction activity. Ca[superscript]2[superscript]+ binding to troponin induces a conformational change that leads to a process of muscle contraction [8].  The focus of our research has been to investigate thermodynamic binding properties of various divalent metals to the Troponin C subunit of the cardiac muscle protein using isothermal titration calorimetry. We have been able to successfully observe Ca[superscript]2[superscript]+ binding to the apo form of Bovine Cardiac TnC (BVCTnC) as well as the apo form of Human Cardiac TnC (HCTnC).   Familial Hypertrophic Cardiomyopathy, FHCM, is an autosomal dominant genetic disorder. FHCM causes an abnormal cardiac muscle contraction response in patients afflicted with the genetic mutations that result in the disorder. About 1 in 500 people, 0.2%, are afflicted with this disorder. There are many ways to approach treatment for this disease. A treatment that we have considered uses calcium sensitizing drugs. Calcium sensitizing drugs allow troponin to be more sensitive to the presence of calcium which induces cardiac muscle contraction [31].  Another focus of our research is to determine thermodynamic binding properties of calcium sensitizing drugs to troponin using isothermal titration calorimetry. Understanding the thermodynamic properties of drug-protein interaction can help reveal the mechanism of action by which the drug operates. These studies will lead to a better understanding of how calcium sensitizing drugs interact with troponin and determine their practicality in drug design for patients afflicted with familial hypertrophic cardiomyopathies.  en_US
dc.description.degreeM.S.en_US
dc.format.extent115 p.en_US
dc.format.mediumdissertations, academicen_US
dc.identifier.urihttp://hdl.handle.net/10342/2917en_US
dc.publisherEast Carolina Universityen_US
dc.subjectChemistry, Inorganicen_US
dc.subjectInorganic chemistry
dc.subject.lcshHeart--Contraction--Regulationen_US
dc.subject.lcshMuscle contraction--Regulationen_US
dc.subject.lcshProtein bindingen_US
dc.subject.lcshProteinsen_US
dc.subject.lcshMyocardiumen_US
dc.titleThermodynamic Investigation into the Binding Properties of Cardiac Troponin (Human and Bovine)en_US
dc.typeMaster's Thesisen_US

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