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Interactions Between Heme-Globins and Ligands

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abstract
Neuroglobin (Ngb) is a hexacoordinated heme protein closely related to the pentacoordinated hemoglobin (Hb) and myoglobin (Mb) and in the central and peripheral nervous systems with expression in some endocrine tissues.1–5 Ngb is believed to play roles in: sustaining ATP production under anaerobic conditions, detoxifying reactive species (O2 and NO), cellular oxygen homeostasis, and reversible binding of O2 with a higher binding affinity than hemoglobin.6 Tejero et al. previously showed that a mutant form of Ngb reduces nitrite to nitric oxide 50x faster than myoglobin and 500x faster than hemoglobin.7 Ngb also tightly binds to carbon monoxide (CO) with an association rate that is 500x faster than hemoglobin.8 Computational simulations and physical investigations were utilized to analyze the structure and kinetics of neuroglobin and the characteristics causing these phenomena. Molecular dynamics simulations of Mb were used as a control to analyze wild-type oxidized human Ngb and mutants for a total of eighteen 1µs trajectories. Time-resolved absorption spectroscopy and flash photolysis experiments were accomplished with Mb and two Ngb mutants. These studies help identify possible treatments for diseases involving low nitric oxide availability and carbon monoxide poisoning.
subject
contributor
Nelson, Lauren (author)
Kim-Shapiro, Daniel B (committee chair)
Holzwarth, Natalie A W (committee member)
Guthold, Martin (committee member)
date
2019-01-11T09:35:15Z (accessioned)
2018 (issued)
degree
Physics (discipline)
2023-12-30 (liftdate)
embargo
2023-12-30 (terms)
identifier
http://hdl.handle.net/10339/93044 (uri)
language
en (iso)
publisher
Wake Forest University
title
Interactions Between Heme-Globins and Ligands
type
Thesis

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