Bawel sandbox1: Difference between revisions
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== Structure of Hexokinase == | == Structure of Hexokinase == | ||
Hexokinase is composed of an N-terminal regulatory domain and a C-terminal catalytic domain. These two domains are <scene name='Bawel_sandbox1/Hexokinase/2'>joined together by an alpha helix</scene>. The molecular weights of hexokinases are around 100 kD. Each domain weighs about 50kD and contains a glucose binding site. But, only in hexokinase II do both halves have functional active sites. The tertiary structure of hexokinase includes an open alpha/beta sheet. There is a large amount of variation associated with this structure. The ATP-binding domain is composed of five beta sheets and | Hexokinase is composed of an N-terminal regulatory domain and a C-terminal catalytic domain. These two domains are <scene name='Bawel_sandbox1/Hexokinase/2'>joined together by an alpha helix</scene>. The molecular weights of hexokinases are around 100 kD. Each domain weighs about 50kD and contains a <scene name='Bawel_sandbox1/Glucose_binding_site/1'>glucose binding site</scene>. But, only in hexokinase II do both halves have functional active sites. The tertiary structure of hexokinase includes an open alpha/beta sheet. There is a large amount of variation associated with this structure. The ATP-binding domain is composed of <scene name='Bawel_sandbox1/5_beta_sheets/3'>five beta sheets and two alpha helices</scene>. In this open alph/beta sheet four of the beta sheets are parallel and one is in the anitparallel directions. The alpha helices and beta loops connect the beta sheets to produce this open alpha/beta sheet. | ||
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== Mechanism of Hexokinase == | == Mechanism of Hexokinase == | ||
In the first reaction of glycolysis, the gamma-phosphoryl group of an ATP molecule is transferred to the oxygen at the C-6 of glucose. Hexokinase catalyzes this phosphoryl group transfer. To start this reaction, ATP forms a complex with magnesium (II) ion and glucose binds to hexokinase. The magnesium-ATP complex then binds with the hexokinase-glucose complex and forms an intermediate (Zeng, et al. present a picture showing the interctions of brain hexokinase with ATP). Asp 532 and Thr 680 are thought to be involved in binding the magnesium ion in the magnesium-ATP complex [4]. The hydroxyl group on the terminal phosphoryl group of the ATP molecule nucleophilically attacks carbon 6 on glucose. This produces glucose-6-phosphate still bound to hexokinase and ADP still in complex with magnesium ion [5]. Glucose-6-phosphate and the magnesium-ADP complex leave hexokinase. Glucose-6-phosphate and ADP are the products of this reaction. Hexokinase undergoes an induced-fit conformational change when it binds to glucose, which ultimately prevents the hydrolysis of ATP. It also experiences potent allosteric inhibition under physiological concentrations by its immediate products, glucose-6-phosphate [4]. This is a mechanism by which the influx of substrate into the glycolytic pathway is controlled. | In the first reaction of glycolysis, the gamma-phosphoryl group of an ATP molecule is transferred to the oxygen at the C-6 of glucose. Hexokinase catalyzes this phosphoryl group transfer. To start this reaction, ATP forms a complex with magnesium (II) ion and glucose binds to hexokinase. The magnesium-ATP complex then binds with the hexokinase-glucose complex and forms an intermediate (Zeng, et al. present a picture showing the interctions of brain hexokinase with ATP). <scene name='Bawel_sandbox1/Asp_532_and_thr_680/2'>Asp 532 and Thr 680</scene> are thought to be involved in binding the magnesium ion in the magnesium-ATP complex [4]. The hydroxyl group on the terminal phosphoryl group of the ATP molecule nucleophilically attacks carbon 6 on glucose. This produces glucose-6-phosphate still bound to hexokinase and ADP still in complex with magnesium ion [5]. Glucose-6-phosphate and the magnesium-ADP complex leave hexokinase. Glucose-6-phosphate and ADP are the products of this reaction. Hexokinase undergoes an induced-fit conformational change when it binds to glucose, which ultimately prevents the hydrolysis of ATP. It also experiences potent allosteric inhibition under physiological concentrations by its immediate products, glucose-6-phosphate [4]. This is a mechanism by which the influx of substrate into the glycolytic pathway is controlled. | ||
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8.↑ Aleshin A, Malfois M, Liu X, Kim C, Fromm H, Honzatko R, Koch M, Svergun D. Nonaggregating Mutant of Recombinant Human Hexokinase I Exhibits Wild-Type Kinetics and Rod-like Conformations in Solution. Biochem. 1999 Apr 29;38:8359-8366. | 8.↑ Aleshin A, Malfois M, Liu X, Kim C, Fromm H, Honzatko R, Koch M, Svergun D. Nonaggregating Mutant of Recombinant Human Hexokinase I Exhibits Wild-Type Kinetics and Rod-like Conformations in Solution. Biochem. 1999 Apr 29;38:8359-8366. | ||