Tolan, Dean R.Allen, Karen N.Bae, So Young2023-06-212023-06-212022https://hdl.handle.net/2144/46349Ketohexokinase (KHK), in an adenosine triphosphate (ATP) dependent reaction, catalyzes the first reaction in fructose metabolism, which converts the furanose form of D-fructose into fructose-1-phosphate. This enzyme has become a target for pharmacological development against fatty liver and metabolic syndrome. KHK exists in two isoforms, A and C, which differs by alternative splicing of exon 3 which encodes 45 out of 298 amino acids. Normally KHK exists as a homodimer and is comprised of an alpha/beta domain interlocking with a β-clasp domain. For KHK-C, there appear to be at least two conformations of the β-clasp domain. Previous work on KHK-A reveals it does not adopt the same conformations. A structure of the mouse KHK-A in its unliganded form is solved and shows that these two conformations also exist for KHK-A. Furthermore, this property is conserved across species. While crystals of human KHK-A in its unliganded form were grown, a structure was not achieved. However, unpublished structures of human KHK-A in its unliganded form also shows different conformations in β-clasp domain when in juxtaposition with the same enzyme complex with ligands. Defining the role of conformational changes in KHK-A is important, because this isozyme has been reported to have a role in cancer metastasis.en-USAttribution-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nd/4.0/BiochemistryCarbohydrate kinaseFructokinaseInduced-fit mode of bindingKetohexokinasePfkB familyStructure and functionThesis/Dissertation2023-06-140000-0001-6862-7166