Cytomegalovirus Protease

At present a wire frame image of the structure of the cytomegalovirus protease is shown below. There are four monomers that make up the tetrameric protease (shades of green and blue). In each monomer you can see the peptide (green, yellow, brown and red).

The molecule can be rotated at any time by left clicking the mouse on the molecule and dragging the mouse with the left button depressed. Or you can switch on rotation using the buttons below. To return to the original wire-frame structure, use the reload/refresh button on your browser.

Human CMV protease is essential for the production of mature infectious virions, as it performs proteolytic processing near the carboxy terminus (M-site) of the viral assembly protein precursor. hCMV protease is a serine protease, although it has little homology to other clans of serine proteases. The crystal structure of hCMV protease at 2.0 angstroms resolution is shown here in association with a peptide that mimics the viral protein to be cleaved. The inhibitor is bound in an extended conformation, forming an anti-parallel beta-sheet with the protease. Ser 132 and His 63 are found in close proximity in the active site. The structure suggests that the third member of the triad is probably His 157. A dimer of the protease with an extensive interface is found in the crystal structure. The two dimers make fewer contacts with each other.

Using the buttons below, first highlight the peptide using yellow spacefill [ On Off ]. Now highlight serine 132 [ On Off ] (red),  histidine 63 [On Off ] (black) and histidine 157 [On Off ] (grey) using the spacefill buttons. You will see that two of these amino acids make contact with the peptide at a specific site. This is the cleavage site within the peptide. The third, his 157, makes contact with the other two amino acids. Zoom and rotate in to see this better [Zoom out Zoom 200% Zoom 300%   Rotate On Rotate Off ].

Using the buttons highlight all of the other serines [On Off  ] and histidines [On Off ]. You will see that there are many serines and somewhat fewer histidines in each chain but only one serine and two histidines of each chain are involved in catalysis of protein cleavage.

You can now change the color of the whole molecule to show the alpha helices and beta pleated sheets [Ribbons Backbone Strands  ]. The alpha helices are shown in purple and the beta sheets in orange. Random coil is in gray.  Any space-filled structures will disappear at this time. Now highlight the peptide to be cleaved [On Off ] (yellow). You will see that the extended peptide forms a beta sheet with a beta sheet of the enzyme that contains serine 132 [On Off     ]. You can highlight this beta sheet [Space Fill Ribbons Strands Off   ]. Now re-highlight serine 132  [ On Off ].

You can alter the appearance of the four chains of the enzyme using the buttons below

Protein data bank information is here

This application requires a Chime plug-in. Get Chime here

Further changes and selection may be made using the Chime menu. Right click on the molecule to show the Chime menu.

© Richard Hunt, University of South Carolina School of Medicine