A three-dimensional consideration of variant human fibrinogens.
Recently reported X-ray structures for large core fragments derived from human fibrinogen and fibrin make it possible to correlate structural and functional anomalies of known genetic variants. Here we examine a variety of amino acid replacements previously reported for hereditary dysfibrinogenemias, most of which are associated with impaired fibrin polymerization. For many of these we have modeled in the mutant amino acid and considered the structural consequences. We have also examined the cases of a small deletion and a large insertion, as well as the impact of substitutions in the GPRPam ligand that was co-crystallized with fragment double-D.
Center for Molecular Genetics, Univ. California, San Diego, La Jolla 92093-0634, USA.
S J
SJ
Everse
G
G
Spraggon
R F
RF
Doolittle
D019943:Amino Acid Substitution; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry* / Q000235:genetics; D015241:Fibrinogens, Abnormal / Q000737:chemistry; D014644:Genetic Variation; D006801:Humans; D008958:Models, Molecular; D008970:Molecular Weight; D009154:Mutation; D014961:X-Ray Diffraction
D005338:Fibrin Fibrinogen Degradation Products; D015241:Fibrinogens, Abnormal; C036309:fibrin fragment D; D005340:Fibrinogen