Sandbox 42

From Proteopedia

Introduction

Adenylate kinase is a protein that is found in the bacterium yersinia pestis. This protein is an enzyme that converts one molecule of ATP and one molecule of AMP into two molecules of ADP. It consists of two chains, and Chain B. The two chains are identical and so structural elements can be examined by focusing on one chain. The space filling section of the protein is the ligand, which is bound to the active site in this representation.

Structural Elements

The is highlighted here, with alpha helices (shown in green) and beta sheets (blue). are shown in black. These bonds show that the beta sheets are connected in parallel, as the hydrogen bonds are angled and not parallel to one another.

The protein's are shown here in stick/wire form, colored gray, while the are colored brown. It is interesting to see the arrangement of these residues in the protein. The hydrophobic residues lie mostly on the interior of the molecule, with most of the polar and charged residues being on the outside. There also seems to be a pocket in the structure where the outer surface dips in, and polar/charged residues are found lining the outside of this pocket as well. This indicates where the ligand enters the active site from being solvated.

In biological systems the primary solvent is water, so it is helpful to see how water interacts with the protein. molecules are added here to the general secondary structure and colored yellow. It is interesting to see where they are, and where they aren't, within the protein. For starters, water surrounds the outer surface. This is because the protein would be in solution in vivo, so it will almost always be solvated. This can be seen in with the protein shown again in stick and wire representation. What is interesting about these models is that water permeates the molecule at least part way. However, as has just been shown, the path to the active site contains a large number of polar and charged amino acid residues, so this is really not surprising. The solvated ligand enters through the channel where water is still present before it becomes unsolvated, at which point it can bind to the protein.

The and interacting side chains are shown here in stick/wire representation, with the rest of the protein semi-transparent. This view shows how the ligand binds to the protein via interactions with protein side chains, as well as that it binds where we expect from the location of the internal polar and charged residues. are colored purple for this view. This shows some very important information. Three of these residues are bound to the ligand, which show how it is anchored into place to the protein. The other two residues, however, are centered on the chain connecting the two parts of the ligand. Since it is a longer, non-hydrolyzable ligand, no chemistry will happen. However, if it were ATP and AMP that were bound, these two catalytic resides would be positioned over the bond that would be broken to form two molecules of ADP. These two residues are clearly important in facilitating the reaction, either by some electron transfer or a conformational change.