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. 1994 Jul 19;91(15):7296–7300. doi: 10.1073/pnas.91.15.7296

Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII.

V C Yee 1, L C Pedersen 1, I Le Trong 1, P D Bishop 1, R E Stenkamp 1, D C Teller 1
PMCID: PMC44386  PMID: 7913750

Abstract

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'.

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