Adenosine Kinase (AK) is a 2 domain protein that regulates extracellular adenosine levels and intracellular adenylate levels. AK binds 2 different substrates; adensosine triphosphate (ATP) and adenosine. In order for the catalyzed reaction to occur both substrates must be bound along with a Magnesium co-factor. Magnesium helps stabilize the binding sites and anchors ATP inside the protein by forming bonds with the beta and gamma phosphate groups of ATP. In the solved crystal sructure by Mathews, Erion, and Ealick there are 2 molecules of adenosine bound instead of an ATP and an adenosine. As a result the Magnesium is bound by water (as seen at right).
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Domain 1 consists of 9 beta-stands and 8 alpha helices. The resulting beta-sheet creates a large pocket that allows both adenosine molecules and the Magnesium atom to fit tightly and be able to interact (shown at right). Domain 2 consists of 5 beta-strands and 2 alpha-helices. The beta-sheets acts like a cover to the substrate binding sites and prevents solvent from interfereing with the catalyzed reaction. The cover may also help hold the substrates firmly in place as the phosphate is transferred (also shown at right).
To view chain A alone click "A"
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To trace chain A click "T"
To view chain B alone click "B"
To trace chain B click "T:
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As mentioned in the Introduction transferases areable to catalyze the reverse reaction also. In AK, Asp300 has a vital role in both the forward and reverse reactions. Asp300 lies on alpha-helix 11. This helix in centrally located in the protein and just so happens to be right in between both adenosine molecules. Asp300 is the key residue that deprotonates the 5'-hydroxyl group of adensosine which allows the now negatively charged oxygen to attack the gamma phosphate on the ATP (schematic below). After the attack ATP loses a phosphate group and becomes adenosine diphosphate (ADP) and the adenosine becomes adenosine monophosphate (AMP). AK is regulated primarily by competitive inhibition. When there is a higher concentration of ATP than of adenosinve, AK will primary produce ADP and AMP. If there is a shortage of ATP in the cell then AK will start taking phosphate groups from AMP or ADP and tacking them on to ADP to form more ATP.
To view locaction of Asp300 in binding site with ligands click "V"
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