Please do NOT make changes to this Sandbox. Sandboxes 30-60 are reserved for use by Biochemistry 410 & 412 at Messiah College taught by Dr. Hannah Tims during Fall 2012 and Spring 2013.
DescriptionDescription
Adenylate Kinase, also known as ADK, is an phosphotransfer enzyme that catalyzes the reversible transfer of phosphate between ATP and AMP. It plays an important role in cell maintenance and cell growth being involved with energy metabolism, signaling, and nucleotide synthesis. The reaction that takes place during the catalysis is ATP + AMP = 2ADP. The enzyme has two conformations, where the inactive form is open, and the active form is closed. The open conformation allows substrates to bind, and the closed form is when the substrate is already bound, and the catalysis is taking place. The enzyme is found in various organisms, and the following images shows the structure of Adenylate Kinase from Yersinia pestis, also known as yeast.
StructureStructure
Adenylate Kinase is made up of 214 amino acids, and the of the protein can be seen on the right in light blue surrounding the non-hydrolysable substrate analogue (red).
The of the protein contains 12 alpha helices (yellow) and 7 beta sheets (green). This secondary structure is held together by , which are anti-parallel between the beta sheets.
Hydrophobic and Hydrophilic ResiduesHydrophobic and Hydrophilic Residues
The of ADK, seen in gray, is buried in the interior of the protein. While the , all the charged and polar side chains (purple), are on the surface of the protein and exposed. The location of the residues depend on the solvent and the environment that the protein is found in. All the hydrophobic residues aggregate together, and bury themselves in the interior of the protein to minimize their contact with their environment. The hydrophilic residues, on the other hand, is exposed on the surface because the enzyme is in an hydrophilic environment. Although, most of the hydrophilic residues would be exposed, it is possible for some of the to be buried in the interior, but they would interact with each other be stabilized there. There are also hydrophilic residues in the active site of the enzyme, where the ligand binds, to help it enter so that the reaction can take place.
Active SiteActive Site
The active site, like mentioned above, is where the ligand/substrate binds to the enzyme to be catalyzed. In ADK, the (gray, blue, pink), is in the interior of the protein. The pink is where the ligand binds directly. There are six , which are specifically involved in the catalyzes of the substrates forming hydrogen bonds with the ligands, and they are highlighted black on the image. The catalytic residues are all charged residues and include Lysine, Aspartic acid, and Arginine. The other residues also interact with the ligand, but only with weak electrostatic and hydrophobic interactions because they are further away.
SolventSolvent
The , which is water (blue), can be co-crystallized with the enzyme. The water can be found all around the protein but there is also some water molecules in the active site, around the ligand. This further indicates why the hydrophilic residues are found on the surface, and the nonpolar residues are buried away. The water creates a hydrophilic environment, and the hydrophobic residues aggregate together in the interior, and the hydrophobic effect drives the water out. The hydrophilic residues in the active site cause water to be present there, and also make it easier for the ligand to enter. For the most part, there are not water molecules in between the secondary structure because that is where the hydrophobic residues reside, but there are some water molecules in the open spaces of the backbone.
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