Sandbox454
Pembrolizumab as a Programmed Cell Death-1 Antagonist
This is a default text for your page Sandbox454. Click above on edit this page to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue. ContentsStructure and FunctionPembrolizumab, or Keytruda, is an immunoglobulin G4 (IgG4)-kappa humanized monoclonal antibody against the programmed cell death-1 (PD-1) receptor. It is a very compact molecule with an asymmetrical Y-shape. The short compact hinge region inflicts constraints on the molecule that creates the abnormal crystallizable tail region (Fc domain) compared to other immunoglobulin G (IgG) proteins. The Fc domain is glycosylated at both CH2 domains on each chain and one of them is distinctively rotated 120° compared to other similar structures, making the glycan chain more solvent accessible and facing the solvent. IgG4s have a unique function where they form dynamic bispecific antibodies by exchanging half-molecules (one heavy chain/light chain pair) among themselves, called Fab-arm exchange. This makes the molecule particularly unstable and unpredictable as a treatment, but can be conquered by introducing a serine-to-proline mutation at amino acid 228, which prevents Fab-arm exchange and stabilizes the molecule<ref/1>. Pembrolizumab/PD-1 InteractionPemFab/PD-1 InteractionPemFv/PD-1 InteractionMechanismThis is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
| ||||||||||||
References
<references/https://dx.doi.org/10.1080/17425255.2016.1216976>
