Press this button to get started (It will bring up the .pbd file for 33F12).
Shown to the left is a model of the fragment antigen-binding (Fab') domain for 33F12. To view the ribbon structure click here .
The Fab' domain is a general structural motif for all antibodies and consists of two variable regions and two constant regions (shown here is the constant region 1 for the heavy chain). The heavy chain is green and the light chain is blue; the variable regions are towards the top of the page.
This button will limit the view to the variable domains which will be the focus of this presentation.
A catalytic lysine in the heavy chain variable region (Lys H93) is key to Ab 33F12's ability to convert a keytone substrate into the necessary reactive enamine. Here Lys H93 is shown as stick presentation in red.
Click here to convert the image from ribbons to a trace through the alpha carbons. This may help view Lys H93.
Unlike other antibodies, Ab 33F12 may not rely on it complementary determining regions (CDRs) to bind. Remember 33F12 is an antibody that acts more like an enzyme, so in essence the variable regions create an active site which can bind a substrate.
Click here to view the hydrophobic pocket associated with the heavy chain only. The light chain is masked in this view to see the surrounding hydrophobic residues on the heavy chain. The Hydrophobic residues are shown in space-filling form with CPK color scheme.
Click here to view Lys H93 as space-filling within the context of the heavy chain hydrophobic pocket.
This button will place Lys H93 in the context of the light chain hydrophobic pocket.
Together these two hydrophobic areas of the light and heavy chain form a hydrophobic microenvironment that is thought to be responsible for the perturbed pKa of Lys H93 which allows it to be an effective nucleophile in the aldolase reaction. Now lets look at the hydrophobic microenvironment with the trace of the variable chains.
The next page will go into more detail about the hydrophobic microenvironment.
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