A 3-DIMENSIONAL CONSIDERATION OF VARIANT HUMAN FIBRINOGENS

Recently reported X-ray structures for large core fragments derived fr om human fibrinogen and fibrin make it possible to correlate structura l and functional anomalies of known genetic variants'. Here we examine a variety of amino acid replacements previously reported for heredita ry dysfibrinogenemias, most of which are associated with impaired fibr in polymerization. For many of these we have modeled in the mutant ami no acid and considered the structural consequences. We have also exami ned the cases of a small deletion and a large insertion, as well as th e impact of substitutions in the GPRPam ligand that was co-crystallize d with fragment double-D.