Kinases adenylate kinase

Adenosine triphosphate (ATP) is one of the most important cofactors involved in many of the synthetic reactions going on within the cell. Its recent large scale in vitro enzymatic synthesis from adenosine and acetylphosphate is of particular interest. Three enzymes immobilized in polyacrylamide gel were used adenosine kinase, adenylate kinase and acetate kinase (lip. ... 

Hexokinase Pyruvate kinase Adenylate kinase Phosphoglycerate kinase Phosphofructokinase Protease inhibitors Pancreatic trypsin inhibitor Soybean trypsin inhibitor Streptomyces subtilisin inhibitor Nucleases... 

ACETATE KINASE ACETYL-CoA CARBOXYLASE ACETYL-CoA SYNTHETASE N-ACETYLCLUCOSAMINE KINASE ACTIN ATPase ACTOMYOSIN ATPase N-ACYLMANNOSAMINE KINASE ADENINE NUCLEOTIDE TRANSLOCASE ADENOSINE KINASE ADENYLATE KINASE (MYOKINASE) ADENYLYLSULFATE KINASE d-ALANINE-d-ALANINE LIGASE... 

ATP Triphosphate Chain Conformation. Much of the work in the area of ATP triphosphate chain conformation has been performed by Cleland and co-workers (14--16). Their studies on metal(III)ATP interactions with kinases have led to the classification of kinases according to the stereochemistry of the polyphosphate chain as it binds to the active site. For the kinases they studied (hexokinase, glycerokinase, creatine kinase, phosphofructokinase, 3-phosphoglycerate kinase, acetate kinase, arginine kinase, adenylate kinase and pyruvate kinase) it was found that B, y-bidentate chromi M(III)-ATP (CrATP) and not a,6,y-tridentate CrATP is a... 

Kinases Direct transfer of terminal phosphoryl group of ATP to substrate Creatine kinase Adenylate kinase Hexokinasc Phosphoglycerate kinase Pyruvate kinase Protein kinase Myokinase Phosphofructokinase Type 1 (M-S-E) Type 1 Type 1 Type 1 Type 2 (S-M-E)... 

The first technique is very intuitive. Out of the few proteins that could be crystallized in a number of different conformations, adenylate kinase is probably the best-studied example. By combining nine observed crystal structures and interpolating between them, a movie was constructed that visualized a hypothetical path of its hinge-bending transition (jVonrhein et al. 1995]). 

To facilitate conformational transitions in the before-mentioned adenylate kinase, Elamrani and co-workers scaled all atomic masses by a large factor thus allowing the use of a high effective simulation temperature of 2000K ([Elamrani et al. 1996]). To prevent protein unfolding, elements of secondary structure had to be constrained. 

Elamrani et al. 1996] Elamrani, S., Berry, M.B., Phillips Jr., G.N., McCammon, J.A. Study of Global Motions in Proteins by Weighted Masses Molecular Dynamics Adenylate Kinase as a Test Case. Proteins 25 (1996) 79-88 [Elcock et al. 1997] Elcock, A.H., Potter, M.J., McCammon, J.A. Application of Poisson-Boltzmann Solvation Forces to Macromolecular Simulations. In Computer Simulation of Biomoleeular Systems, Vol. 3, A.J. Wilkinson et al. eds., ESCOM Science Publishers B.V., Leiden... 

Figure 4.14 Examples of different types of open twisted a/p structures. Both schematic and topological diagrams are given. In the topological diagrams, arrows denote strands of p sheet and rectangles denote a helices, (a) The FMN-binding redox protein flavodoxln. (b) The enzyme adenylate kinase, which catalyzes the reaction AMP +...

The second structure, adenylate kinase (Figure 4.14b), has two such posi-I tions, one on each side of p strand 1. The connection from strand 1 to strand 12 goes to the right, whereas the connection from the flanking strands 3 and 4 both go to the left. Crevices are formed between p strands 1 and 3 and [between strands 1 and 4. One of these crevices forms part of an AMP-binding [site, and the other crevice forms part of an ATP-binding site that catalyzes the Iformation of ADP from AMP and ATP. 

AMP reverses the inhibition due to ATP, and AMP levels in cells can rise dramatically when ATP levels decrease, due to the action of the enzyme adenylate kinase, which catalyzes the reaction... 

Adenylate kinase rapidly interconverts ADP, ATP, and AMP to maintain this equilibrium. ADP levels in cells are typically 10% of ATP levels, and AMP levels are often less than 1% of the ATP concentration. Under such conditions, a small net change in ATP concentration due to ATP hydrolysis results in a much larger relative increase in the AMP levels because of adenylate kinase activity. 

The problem can be solved using the equilibrium expression for the adenylate kinase reaction ... 

Mitochondria are surrounded by a simple outer membrane and a more complex inner membrane (Figure 21.1). The space between the inner and outer membranes is referred to as the intermembrane space. Several enzymes that utilize ATP (such as creatine kinase and adenylate kinase) are found in the intermembrane space. The smooth outer membrane is about 30 to 40% lipid and 60 to 70% protein, and has a relatively high concentration of phos-phatidylinositol. The outer membrane contains significant amounts of porin —a transmembrane protein, rich in /3-sheets, that forms large channels across the membrane, permitting free diffusion of molecules with molecular weights of about 10,000 or less. Apparently, the outer membrane functions mainly to... 

The lower panel shows the decreasing concentration of ATP, to about 60% of resting levels, and the simultaneous equimolar increase in IMP. The fall in ATP started when most of the PCr store was utilized, resulting in a decreased rate of ADP phosphorylation via the creatine kinase reaction. The resultant accumulation of ADP stimulates adenylate kinase activity and subsequently IMP is formed via the AMP deaminase reaction ... 

Adenosine 5 -hypophosphate (23), an analogue of ADP, can undergo phosphorylation by PEP and pyruvate kinase to yield (24). Adenylate kinase which catalyses the scission of the bond between the a and j8 phosphorus atoms in ADP is, not surprisingly, inhibited competitively by (23). 

Comparison with the nucleotide binding sites in adenylate kinase... 

Maker, H.S. Weiss, C. and Brannan. Amine-mediated toxicity The effects of dopamine, norepinephrine, 5-hydroxytryptamine, 6-hydroxy-dopamine, ascorbate, glutathione and peroxide on the in vitro activities of creatine and adenylate kinases in the brain of the rat. 

Adenylate kinase (AK) is a ubiquitous monomeric enzyme that catalyzes the interconversion of AMP, ADP, and ATP. This interconversion of the adenine nucleotides seems to be of particular importance in regulating the equilibrium of adenine nucleotides in tissues, especially in red blood cells. AK has three isozymes (AK 1,2, and 3). AK 1 is present in the cytosol of skeletal muscle, brain, and red blood cells, and AK 2 is found in the intermembrane space of mitochondria of liver, kidney, spleen, and heart. AK 3, also called GTP AMP phosphotransferase, exists in the mitochondrial matrix of liver and heart. 

B15. Beutler, E., Carson, D., Dannawi, H., Forman, L., Kuhl, W., West, C., and Westwood, B., Metabolic compensation for profound erythrocyte adenylate kinase deficiency A hereditary enzyme defect without hemolytic anemia. J. Clin. Invest. 72,648-655 (1983). 

B33. Boivin, P, Galand, C Hakim, J., Simony, J., and Seligman, M., Une nouvelle erythroenzy-mopathies Anemie hemolytique congenitale non spherocytaire et deficit hereditaire en adenylate-kinase erythrocytaire. Presse Med. 79,215-218 (1971). 

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