Sandbox Reserved 401: Difference between revisions
No edit summary |
No edit summary |
||
| Line 23: | Line 23: | ||
== Structure == | == Structure == | ||
The structure of hexokinase was first determined from yeast by Tom Steitz at Yale University. This compound is composed of a large homodimer of 920 amino acids in each chain. Each chain is about equal molecular weights. Hexokinase has a tertiary structure which includes an open alpha/beta sheet. There is a lot of variation associated with this structure. It’s composed of three alpha helices, and five beta sheets. The open beta sheet is composed of four parallel sheets, and one antiparallel sheet. The beta loops | The structure of hexokinase was first determined from yeast by Tom Steitz at Yale University. This compound is composed of a large homodimer of 920 amino acids in each chain. Each chain is about equal molecular weights. Hexokinase has a tertiary structure which includes an open alpha/beta sheet. There is a lot of variation associated with this structure. It’s composed of three alpha helices, and five beta sheets. The open beta sheet is composed of four parallel sheets, and one antiparallel sheet. The beta loops connect the alpha helices and beta sheets to produce this open alpha/beta sheet. Hexokinase is capable of binding two ligands, glucose, and glucose-6-phosphate.<ref> Schneeberger M.B. Biophysical Chemistry 406.Hexokinase Structure.1999; [http://www.chem.uwec.edu/Webpapers_F99/Pages/Webpapers_F99/schneebm/Pages/structure.html] </ref> | ||
'''Active Sites''' | '''Active Sites''' | ||
The active site residues for Hexokinase are Asp205, Lys169, Asn204, Glu256,and Thr168. <ref> Koshland D. Induced Fit and Hexokinase.Fig.7 Active Site of Glucokinase/Hexokinase.2010; [http://www.chem.ucsb.edu/~molvisual/ABLE/induced_fit/index.html] </ref> These residues are located in the deep cleft at the interface between the two lobes. This active site is cable of bonding two ligands, glucose, and glucose-6-phosphate. Hexokinase undergoes an induced fit conformational change when glucose binds. This conformational change prevents the hydrolysis of ATP,and is allosterically inhibited by physiological concentrations of glucose-6-phosphate the product. Hexokinase has two conformational states. The open state occurs prior to glucose binding. ATP is bound to the large lobe, but is far away from the glucose binding site, and in a different position than it assumes in the active site. When the glucose binds to Hexokinase a large conformational change occurs. This change closes the two lobes around the glucose substrate. This conformational state is the closed state. <ref> Kitto B.G, Caras J., Caras P. Interactive Concepts in Biochemistry. Structural Tutorials.2008; Chp: 15.1, 15.5. [ http://higheredbcs.wiley.com/legacy/college/boyer/0471661791/structure/hexokinase/hexokinase.htm] </ref> | The active site residues for Hexokinase are Asp205, Lys169, Asn204, Glu256,and Thr168. <ref> Koshland D. Induced Fit and Hexokinase.Fig.7 Active Site of Glucokinase/Hexokinase.2010; [http://www.chem.ucsb.edu/~molvisual/ABLE/induced_fit/index.html] </ref> These residues are located in the deep cleft at the interface between the two lobes. This active site is cable of bonding two ligands, glucose, and glucose-6-phosphate. Hexokinase undergoes an induced fit conformational change when glucose binds. This conformational change prevents the hydrolysis of ATP, and is allosterically inhibited by physiological concentrations of glucose-6-phosphate the product. Hexokinase has two conformational states. The open state occurs prior to glucose binding. ATP is bound to the large lobe, but is far away from the glucose binding site, and in a different position than it assumes in the active site. When the glucose binds to Hexokinase a large conformational change occurs. This change closes the two lobes around the glucose substrate. This conformational state is referred to as the closed state. <ref> Kitto B.G, Caras J., Caras P. Interactive Concepts in Biochemistry. Structural Tutorials.2008; Chp: 15.1, 15.5. [ http://higheredbcs.wiley.com/legacy/college/boyer/0471661791/structure/hexokinase/hexokinase.htm] </ref> | ||
The active site residues in the open conformational structure for hexokinase are far away from the ligand binding site. <scene name='Sandbox_Reserved_401/Active_sites_and_ligand/1'>Active Sites (GREEN)Ligands(YELLOW)</scene> | The active site residues in the open conformational structure for hexokinase are far away from the ligand binding site. <scene name='Sandbox_Reserved_401/Active_sites_and_ligand/1'>Active Sites (GREEN)Ligands(YELLOW)</scene> | ||