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Homology Modeling and Domain Interactions in Fetal Serum Protein Alphafetoprotein
 
 
Authors          Audiences          Overview           Materials          Resources           Future Directions
 

 


Authors


Steve Festin
Hamilton College

 
   
 


Possible Audiences:

Undergraduate Biochemistry (mid-level)  

 
 


Brief Overview

This exercise is intended to engage students to design, model, visualize and evaluate the theoretical three dimensional image of a protein whose structure has not yet been determined. The phylogenetic analysis in Biology Workbench (See files attached) of paralogs and orthologs to alphafetoprotein reveals more divergent sequences within active site domains of related proteins without biological activity and greater conservation of the alphafetoprotein active domain between different species.  

 
   
 


Project Materials

Materials include two segments. Part 1 includes a modeling request to Swiss-Model at expasy.ch; Part 2 Includes installing and using a visualization tool, Swiss-PDB viewer, to orient and highlight portions of the molecule, then thermodynamic minimization to identify residues distorted in the homology model construction.  

 
 


Resources and References

AFP Specific: Festin, S. M., J. A. Bennett, et al. (1999). "The recombinant third domain of human alpha-fetoprotein retains the antiestrotrophic activity found in the full-length molecule." Biochim Biophys Acta 1427(2): 307-14.

Mesfin, F. B., J. A. Bennett, et al. (2000). "Alpha-fetoprotein-derived antiestrotrophic octapeptide." Biochim Biophys Acta 1501(1): 33-43.

Mizejewski, G. J. (1995). "Alpha-fetoprotein binding proteins: implications for transmembrane passage and subcellular localization." Life Sci 56(1): 1-9.

 

 
   
 


Future Directions

Execise is currently under development to include an exploratory module to investigate evolutionary relationships between alphafetoprotein and its cellular partners Afamin, Vitamin D Binding Protein and Albumin among a number of differnet species.  

 
 


Attachments


- Model_Construct.doc
- Swiss-Model_Request.doc
- ALBHUM_para_clustw.pdf
- FETA_ortho_clustw.pdf