Structure analysis and homology modeling of carcinoembryonic antigen
Carcinoembryonic antigen (CEA), a highly glycosylated cell surface protein is a widely distributed tumour marker. Although it is expressed in high
proportions on a variety of human tumours, notably of the colon but also of the breast and lung, studies also reveal the presence of CEA in normal tissues.
Thus the distribution and possibly the functional role of CEA is complex. Monoclonal antibodies (Mabs) against CEA have been used successfully for
redioimmuno-localization of tumors. However, little progress has been made towards mapping the exact locations of these Mab’s to the surface of CEA. A carefully constructed epitope map should help to probe the function(s) and help in the search for Mab’s with greater binding affinity to this important tumour marker.
Prediction of the CEA 3D structure
The mature
CEA (CEAM5_HUMAN) consists of 668 amino acids. The extracellular
region (35-677) consists of seven domains, each having sequence similarity
with immunoglobulin (Ig) domains. The sequence relationship with
the immunoglobulins suggests that the complete extracellular region
can be modelled with some confidence from Ig folds with know 3D structures.
It is possible to prediction the 3D structure of each of the seven
domains based on knowledge-based
homology modelling. A possible packing model between each of the
seven domains can be proposed and candidate residues can be labelled
for site-directed mutagenesis.