Sandbox 50: Difference between revisions

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OCA, Student, Natalie Ziegler, Hannah Tims

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-<applet load='1QLQ' size='300' frame='true' align='right' caption='Insert caption here' />
+<Structure load='1AKE' size='500' frame='true' align='right' caption='Adenylate_Kinase ' scene='Insert optional scene name here'/>
-=Trypsin=
-Trypsin is a medium sized, globular, digestive serine protease that is synthesized by the pancreas and secreted into the duodenum of the small intestine. Trypsin hydrolyzes peptide bonds based on side chain specificities of the amino acids surrounding the bond to be cleaved. Trypsin's specificity is for the positively charged side chains of lysine and arginine.
+==Description==
+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.
 ==Structure==
-Trypsin's primary structure is a polypeptide chain of 237 amino acids. These amino acids interact with each other mostly through hydrogen bonding to form trypsin's secondary structural units. Trypsin has many important <scene name='Sandbox_50/Secondarystructure/1'>secondary structural elements</scene>, including two alpha helices (blue), an anti-parallel beta sheet (green), and random coils (gray). The arrows on these elements point toward the carboxy terminus of the protein. These secondary structures interact together to form the fully folded, native trypsin.
-===Polar and Nonpolar Residues===
+Adenylate Kinase is made up of 214 amino acids, and the <scene name='Sandbox_50/Ak_backbone/1'>backbone</scene> of the protein can be seen on the right in light blue surrounding the non-hydrolysable substrate analogue (red).
-Trypsin's distribution of <scene name='Sandbox_50/Nonpolarandpolar/1'>polar and nonpolar residues</scene> follow the rules of the hydrophobic effect. The nonpolar (gray) residues are located on the interior of the protein so they can be shielded from water, while the polar (purple) residues are distributed on the exterior of the protein because they can interact with water. This <scene name='Sandbox_50/Nonpolarandpolarspacefilled/1'>spacefill</scene> model shows the distribution of the hydrophilic and hydrophobic residues and the actual space they occupy. Again the hydrophobic, nonpolar residues are shown in gray, and the hydrophilic, polar residues are purple. This type of residue distribution in trypsin is entropically favorable becuase the water surrounding the protein does not become ordered. In this figure the <scene name='Sandbox_50/Polarwater/1'>polar residue interaction with water</scene> can be seen. The puprle polar residues are the residues that are interacting with the red water molecules.
+The <scene name='Sandbox_50/Ak_secondary_structure/1'>secondary_structure</scene> of the protein contains 12 alpha helices (yellow) and 7 beta sheets (green). This secondary structure is held together by <scene name='Sandbox_50/Ak_hydrogen_bonds/1'>hydrogen_bonds</scene>, which are anti-parallel between the beta sheets. This hydrogen bond network also assists in the flexibility of the enzyme.
-==Attractions Between Structural Components and the Remainder of the Protein==
-===Disulfide Bonds===
+==Hydrophobic and Hydrophilic Residues==
-Trypsin contains three <scene name='Sandbox_50/Disulfidebonds/1'>disulfide bonds</scene> involving six cysteine residues. These disulfide bonds are intramolecular forces that stabalize the tertiary structure of Trypsin. The figure shows the yellow disulfide bonds between the cysteine residues connecting two random coils, connecting one of the alpha helices to the beta sheet, and the other disulfide connecting the two alpha helices.
-===Residue Charge===
+The <scene name='Sandbox_50/Ak_hydrophobic_residues/1'>hydrophobic_residues</scene> of ADK, seen in gray, is buried in the interior of the protein. While the <scene name='Sandbox_50/Ak_hydrophiblic_residues2/1'>hydrophilic_residues</scene>, 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.
-This <scene name='Sandbox_50/Charged/1'>charge figure</scene> shows the different charges of the amino acid residues that make up Trypsin. The blue residues have cationic side chains, the red residues have anionic side chains, the light purple are the polar, uncharged residues, and the gray residues are hydrophobic. When compared to the spacefilled figure above, the direct correlation between polarity of the side chain and charge of the side chain can be seen. Those residues with charged (blue and red) side chains as well as the polar, uncharged residues are the residues on the exterior of the protein, while the hydrophobic residues remain at the protein's core. Those residues that are cationic and anionic are able to participate in salt bridges.
-==Ligand Contacts==
+==Active Site==
+The active site, like mentioned above, is where the substrates binds to the enzyme to be catalyzed. In ADK, the <scene name='Sandbox_50/Ak_ligand_contact1/1'>ligand_contacts</scene> (gray, blue, pink), is in the interior of the protein. The pink is where the ligand binds directly. There are mostly hydrophilic residues present in the active site because water enters the active site regularly it causes the hydrophobic residues to still be buried within the protein. But there are some hydrophobic interactions that take place between the enzyme and the substrates, which helps stabilizes the substrate in the site, so that it can be catalyzed. There are six <scene name='Sandbox_50/Ak_catalytic_residues1/1'>catalytic_residues</scene>, which are highlighted black on the image, and they are specifically involved in the catalyzes of the substrates forming hydrogen bonds with the substrate. The catalytic residues are all charged residues and include Lysine, Aspartic acid, and Arginine. These residues also allow for electrostatic interactions but can be effected by the presence of the water in the active site.
+==Solvent==
+The <scene name='Sandbox_50/Ak_water6/1'>solvent</scene>, 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, which is the hydrophobic effect and drives the water out. So for the most part, there are not water molecules in between the secondary structure, but there are some water molecules in the open spaces between the backbone.The hydrophilic residues in the active site allow water to be present, and also make it easier for the substrates to enter and facilitates in the catalysis.
+==References==
+http://www.ncbi.nlm.nih.gov/pubmed/21365689
+http://medical-dictionary.thefreedictionary.com/adenylate+kinase
+http://en.wikipedia.org/wiki/Adenylate_kinase
+http://www.ebi.ac.uk/interpro/IEntry?ac=IPR007862
+http://www.whatislife.com/reader/interaction-reader.html
+Voet, D., Voet, J., and Pratt, C. W. ''Fundamentals of Biochemistry: Life at the Molecular Level''. 3rd Edition. (2008)