Sandbox 172: Difference between revisions
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==Structural Overview== | ==Structural Overview== | ||
The size of hexokinase type I is approximately 100 kD.<ref>Fromm H., Zewe V. Kinetic studies of the brain hexokinase reaction. The Journal of Biological Chemistry. 1962.'''235''':1661-1667.</ref> Hexokinase type I is constructed by a N-terminal regulatory domain and a C-terminal catalytic domain joined together by an [http://en.wikipedia.org.wiki/alpha_helix alpha helix]. The glucose binding site of hexokinase type I can be found within the two sub-units that make up the isoenzyme, these are known as lobes. Factors that contribute to the binding of glucose to this active site include amino acids within the actual site and [http://en.wikipedia.orh.wiki/hydrogen_bong hydrogen bonding] that takes place on the glucose between the hydroxyl groups.<ref>Bianchi M., Bolognesi M., Deriu D., Magnani M., Murshudov G., Rizzi M., Rosano C., Sabini E., Serafini G. Binding of non-catalytic ATP to human hexokinase I highlights the structural components for enzyme-membrane association control. Structure. 1999. '''11''': 1427-1437. PMID [http://www.ncbi.nlm.nih.gov/pubmed/10574795?dopt=Abstract 10574795]</ref> | The size of hexokinase type I is approximately 100 kD.<ref>Fromm H., Zewe V. Kinetic studies of the brain hexokinase reaction. The Journal of Biological Chemistry. 1962.'''235''':1661-1667.</ref> Hexokinase type I is constructed by a N-terminal regulatory domain and a C-terminal catalytic domain joined together by an [http://en.wikipedia.org.wiki/alpha_helix alpha helix]. The glucose binding site of hexokinase type I can be found within the two sub-units that make up the isoenzyme, these are known as lobes. Factors that contribute to the binding of glucose to this active site include amino acids within the actual site and [http://en.wikipedia.orh.wiki/hydrogen_bong hydrogen bonding] that takes place on the glucose between the hydroxyl groups.<ref>Bianchi M., Bolognesi M., Deriu D., Magnani M., Murshudov G., Rizzi M., Rosano C., Sabini E., Serafini G. Binding of non-catalytic ATP to human hexokinase I highlights the structural components for enzyme-membrane association control. Structure. 1999. '''11''': 1427-1437. PMID [http://www.ncbi.nlm.nih.gov/pubmed/10574795?dopt=Abstract 10574795]</ref> | ||
[[Image:Hexlobes.jpg|thumb|right|The C-terminal and N-terminal regions of Hexokinase Type I - held together by hydrogen bonding and a connecting helix.<ref>Hay N., Robey R. Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene. 2006. '''25''': 4683-4696.</ref>]] | [[Image:Hexlobes.jpg|thumb|right|'''Figure 2:'''The C-terminal and N-terminal regions of Hexokinase Type I - held together by hydrogen bonding and a connecting helix.<ref>Hay N., Robey R. Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene. 2006. '''25''': 4683-4696.</ref>]] | ||
===Glucose Binding Sites=== | ===Glucose Binding Sites=== | ||
The residues of the glucose binding site of Hexokinase Type I are very highly conserved within the hexokinase sequence; glucose binds equally to both domains or "lobes" of the structure. As a result, hexokinase type I in its native conformation has an active site in its inactive regulatory domains. Before glucose binds to hexokinase type I, it is said to be in an open conformation. ATP is already bound within one of the domains but it is situated a distance from the glucose binding site. As the glucose binds, the two domains close around the glucose substrate and this change results in a newly formed pattern of hydrogen bonding.<ref name="one" /> | The residues of the glucose binding site of Hexokinase Type I are very highly conserved within the hexokinase sequence; glucose binds equally to both domains or "lobes" of the structure. As a result, hexokinase type I in its native conformation has an active site in its inactive regulatory domains. Before glucose binds to hexokinase type I, it is said to be in an open conformation. ATP is already bound within one of the domains but it is situated a distance from the glucose binding site. As the glucose binds, the two domains close around the glucose substrate and this change results in a newly formed pattern of hydrogen bonding.<ref name="one" /> | ||
[[Image:Glucosebinding.jpg|thumb|left|The conformational change in hexokinase caused by glucose binding.<ref>Martin D., Huang P., Pelicano H., Xu R. Glycolysis inhibition for anticancer treatment. Oncogene. 2006. '''25''': 4633-4646.</ref>]] | [[Image:Glucosebinding.jpg|thumb|left|'''Figure 3:'''The conformational change in hexokinase caused by glucose binding.<ref>Martin D., Huang P., Pelicano H., Xu R. Glycolysis inhibition for anticancer treatment. Oncogene. 2006. '''25''': 4633-4646.</ref>]] | ||
===Active Site=== | ===Active Site=== | ||
In the <scene name='Sandbox_172/Mynewscene/2'>active site</scene> of hexokinase type I, <scene name='Sandbox_172/Residue1/4'>Lys 621</scene>-denoted in red, and <scene name='Sandbox_172/Residue1/5'>Asp 657</scene>-denoted in blue, show the hydrogen-bonding distance in which a reactive O6 hydroxyl is situated in between. Here Lys 621 functions to aid the transfer of the phosphate moiety which is negatively charged; Asp 657 serves as a catalytic base or to position the glucose O6 correctly for phosphoryl transfer to take place.<ref name="one" /> Though it may seem that | In the <scene name='Sandbox_172/Mynewscene/2'>active site</scene> of hexokinase type I, <scene name='Sandbox_172/Residue1/4'>Lys 621</scene>-denoted in red, and <scene name='Sandbox_172/Residue1/5'>Asp 657</scene>-denoted in blue, show the hydrogen-bonding distance in which a reactive O6 hydroxyl is situated in between. Here Lys 621 functions to aid the transfer of the phosphate moiety which is negatively charged; Asp 657 serves as a catalytic base or to position the glucose O6 correctly for phosphoryl transfer to take place.<ref name="one" /> Though it may seem that | ||
