Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII.
Mechanical stability in many biological materials is provided by the crosslinking of large structural proteins with gamma-glutamyl-epsilon-lysyl amide bonds. The three-dimensional structure of human recombinant factor XIII (EC 2.3.2.13 zymogen; protein-glutamine:amine gamma-glutamyltransferase a chain), a transglutaminase zymogen, has been solved at 2.8-A resolution by x-ray crystallography. This structure shows that each chain of the homodimeric protein is folded into four sequential domains. A catalytic triad reminiscent of that observed in cysteine proteases has been identified in the core domain. The amino-terminal activation peptide of each subunit crosses the dimer interface and partially occludes the opening of the catalytic cavity in the second subunit, preventing substrate binding to the zymogen. A proposal for the mechanism of activation by thrombin and calcium is made that details the structural events leading to active factor XIIIa'.
Yee
V C
VC
Department of Biochemistry, University of Washington, Seattle 98195.
Pedersen
L C
LC
Le Trong
I
I
Bishop
P D
PD
Stenkamp
R E
RE
Teller
D C
DC
D002384:Catalysis; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D006801:Humans; D011487:Protein Conformation; D017510:Protein Folding; D011503:Transglutaminases / Q000737:chemistry* / Q000378:metabolism
D011503:Transglutaminases