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090 a| QP113.2;

100 1 a| Haulsee, Zachary Merle.?| UNAUTHORIZED;

245 10 a| Thermodynamic investigation into the binding properties of cardiac troponin (human and bovine) /c| by Zachary Merle Haulsee.;

260 a| [Greenville, N.C.] :b| East Carolina University,c| 2010.;

300 a| 115 pages :b| illustrations (some color), digital, PDF file;

336 a| text2| rdacontent;

337 a| computer2| rdamedia;

338 a| online resource2| rdacarrier;

500 a| Presented to the faculty of the Department of Chemistry.;

500 a| Advisor: Anne Spuches.;

500 a| Title from PDF t.p. (viewed Jan. 4, 2011).;

502 b| M.S.c| East Carolina Universityd| 2010.;

504 a| Includes bibliographical references.;

520 3 a| Troponin is an integral protein in the mechanism of muscle contraction. In order to induce cardiac muscle contraction, Ca²[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 Ca²[superscript]+ and Myosin. Ca²[superscript]+ greatly increases the rate of ATPase activity (18-fold) and decreases the concentration of actin needed for muscle contraction activity. Ca²[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 Ca²[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.;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

650 0 a| Heartx| Contractionx| Regulation.=| ^A1036901;

650 0 a| Muscle contractionx| Regulation.=| ^A988617;

650 0 a| Protein binding.=| ^A12889;

650 0 a| Proteins.=| ^A2392;

650 0 a| Myocardium.=| ^A3434;

653 a| Chemistry, Inorganic;

700 1 a| Spuches, Anne M.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Chemistry.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/2917;

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999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 2329408-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 11/3/2010x| ETDz| HERESOURCE;

Thermodynamic investigation into the binding properties of cardiac troponin (human and bovine) / by Zachary Merle Haulsee.

Author/creator	Haulsee, Zachary Merle
Other author	Spuches, Anne M.
Other author	East Carolina University. Department of Chemistry.
Format	Theses and dissertations
Publication Info	[Greenville, N.C.] : East Carolina University, 2010.
Description	115 pages : illustrations (some color), digital, PDF file
Supplemental Content	Access via ScholarShip
Subjects	Heart--Contraction. --Regulation. Muscle contraction--Regulation. Protein binding. Proteins. Myocardium.

Summary	Troponin is an integral protein in the mechanism of muscle contraction. In order to induce cardiac muscle contraction, Ca²[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 Ca²[superscript]+ and Myosin. Ca²[superscript]+ greatly increases the rate of ATPase activity (18-fold) and decreases the concentration of actin needed for muscle contraction activity. Ca²[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 Ca²[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.
General note	Presented to the faculty of the Department of Chemistry.
General note	Advisor: Anne Spuches.
General note	Title from PDF t.p. (viewed Jan. 4, 2011).
Dissertation note	M.S. East Carolina University 2010.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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