Structural and functional analysis of proximal pocket mutants of sperm whale myoglobin

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dc.contributor.advisorPhillips, George N., Jr.en_US
dc.creatorLiong, Elaine Chiuen_US
dc.date.accessioned2009-06-04T06:40:03Zen_US
dc.date.available2009-06-04T06:40:03Zen_US
dc.date.issued1999en_US
dc.description.abstractMyoglobin is the subject of continuing investigations because of its ability to bind oxygen reversibly. This physiological role depends on the modulation of iron reactivity and heme affinity by the globin. The hypothesis that both of these factors are affected by residues in the proximal heme pocket is tested by site-directed mutagenesis of four proximal residues: Leu89(F4), His97(FG3), His99(FG5), and Leu104(G5). The structures of several mutant myoglobins have been determined by X-ray crystallography and then used to interpret the results of functional studies. These four proximal pocket residues support and maintain the structure of the porphyrin ring via steric and/or electrostatic interactions with the heme prosthetic group. In turn, stereochemical changes in the heme group induced by a proximal pocket mutation modulate heme-iron reactivity via changes in the displacement of the iron from the heme plane: a more accessible heme iron results in greater affinity for carbon monoxide and dioxygen. Leu89 and His97 are important surface residues that protect the hydrophobic heme pocket from hydration through steric and/or electrostatic interactions with the heme. Substitutions at either position with a small or polar residue expose the heme pocket to solvent and accelerate heme loss. Ile99 and Leu104 are located in the interior region of the heme pocket beneath the heme prosthetic group. Substitution with smaller or polar residues at positions 99 and 104 also results in water penetration of the heme pocket and promotion of heme loss. Furthermore, Leu104 is located between two sites previously found to bind xenon. Crystal structures of xenon-containing Leu104 mutant myoglobins support the hypothesis that changes in the volume accessible to photodissociated ligands affects the rates of primary and secondary recombination.en_US
dc.format.extent113 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS BIOCHEM. 1999 LIONGen_US
dc.identifier.citationLiong, Elaine Chiu. "Structural and functional analysis of proximal pocket mutants of sperm whale myoglobin." (1999) Diss., Rice University. <a href="https://hdl.handle.net/1911/19401">https://hdl.handle.net/1911/19401</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/19401en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectBiophysicsen_US
dc.titleStructural and functional analysis of proximal pocket mutants of sperm whale myoglobinen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBiochemistry and Cell Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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