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Proc Natl Acad Sci U S A. 1978 October; 75(10): 4848–4852. | PMCID: PMC336218 |
Glucose-induced conformational change in yeast hexokinase. W S Bennett, Jr and T A Steitz Abstract The A isozyme of yeast hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) crystallized as a complex with glucose has a conformation that is dramatically different from the conformation of the B isozyme crystallized in the absence of glucose. Comparison of the high-resolution structures shows that one lobe of the molecule is rotated by 12 degrees relative to the other lobe, resulting in movements of as much as 8 A in the polypeptide backbone and closing the cleft between the lobes into which glucose is bound. The conformational change is produced by the binding of glucose (R.C. McDonald, T.A. Steitz, and D.M. Engelman, unpublished data) and is essential for catalysis [Anderson, C.M., Stenkamp, R.E., McDonald, R.C. & Steitz, T.A. (1978) J. Mol. Biol. 123, 207-219] and thus provides an example of induced fit. The surface area of the hexokinase A-glucose complex exposed to solvent is smaller than that of native hexokinase B. By using the change in exposed surface area to estimate the hydrophobic contribution to the free energy changes upon glucose binding, we find that the hydrophobic effect alone favors the active conformation of hexokinase in the presence and absence of sugar. The observed stability of the inactive conformation of the enzyme in the absence of substrates may result from a deficiency of complementary interactions within the cavity that forms when the two lobes close together. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. These references are in PubMed. This may not be the complete list of references from this article. - Kaji A, Colowick SP. Adenosine triphosphatase activity of yeast hexokinase and its relation to the mechanism of the hexokinase reaction. J Biol Chem. 1965 Nov;240(11):4454–4462. [PubMed]
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