Active Site Models

The HIV Protease Active Site or, "the Catalytic Cube".

We have modeled the twenty-five Angstrom cube of space centered around the active site of this protease. Eight separate loops of protein structure....in an alpha-carbon backbone format...we constructed and glued to the inside of an acrylic cube. A laser engraver was used to trace the precise intersections of each backbone element on the various faces of the cube. Holes were built into each alpha carbon to allow for the addition of amino acid sidechains, constructed from commercial modeling kits scaled at 1cm /Angstrom. The front, back and top of the cube were cut out to allow physical access to the model. An inhibitor of this active site was then modeled in a ball-and-stick format, and positioned in the active site.

The Chymotrypsin Active Site or "the active site plate".

We have modeled the chymotrypsin active site, with its classic "catalytic triad" of active site sidechains modeled in a ball-and-stick format. This model represents a "slab" through the protein that was oriented so as to retain the elements of protein structure that contribute the three active site residues.

Of these three active site residues (His57, Asp102 and Ser195) we noticed that Asp102 is portioned in the active site by a 24 amino acid loop of structure that completes a 6-stranded beta sheet in the protein. As an educational exercise, we have developed a flexible protein modeling system that allows the tactile exploration of 3D space available to a specific loop of structure. In a classroom setting, this model can be used to illustrate the importance of protein secondary structure in stabilizing loops of protein structure. In a research setting, this flexible loop will allow investigators to consider possible conformational changes in loops upon substrate binding or phosphorylation.

	Sarah is holding a SLS alpha-carbon backbone model of Chymotripsin highlighting the 24 amino acid loop and the HIS, ASP, SER triad. On the table is the interactive Chymotripsin Active Site Plate.
A detail of the Chymotripsin Active Site plate. Sarah is holding the flexible loop (in grey). It is composed of 24 interlocking pieces which represent alpha-carbon to alpha-carbon links. The 24 pieces are able to rotate about 180° allowing for full flexablity of the protein loop. The units are scaled to 1cm = 1 angstrom.
	The grey flexible loop is bent into one of the may configurations of the protein which would arrange the catalytic triad into the proper configuration. The flexible loop can be replaced with a rigid alpha-carbon backbone structure to illustrate the "correct" folding configuration of the flexible loop.

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