Structure and Function Studies of Factor XIIIa by x-ray Crystallography

Vivien C. Yee; Isolde Le Trong; Paul D. Bishop; Lars C. Pedersen; Ronald E. Stenkamp; David C. Teller

doi:10.1055/s-2007-999035

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 1996; 22(5): 377-384
DOI: 10.1055/s-2007-999035

Structure and Function Studies of Factor XIIIa by x-ray Crystallography

Vivien C. Yee^* , Isolde Le Trong^† , Paul D. Bishop^‡ , Lars C. Pedersen^§ , Ronald E. Stenkamp^† , David C. Teller^*

From the *Biochemistry Department and
†Department of Biological Structure, University of Washington, Seattle, Washington,
‡ZymoGenetics Inc, Seattle, Washington, and
§National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.

Abstract

PDF Download

Abstract

The three-dimensional structures of several forms of the factor XIII A subunit have been determined using single crystal x-ray diffraction methods. Our crystallographic studies have provided the first detailed structural view of the factor XIII A subunit and information that is useful for understanding transglutaminase function. We have identified a conserved Cys314-His373-Asp396 catalytic triad of residues in the active site of the molecule and a number of other conserved residues that may play important roles as well. The calcium and strontium structures have revealed several conserved acidic residues (Asp438, Glu485, and Glu490) involved in ion binding. We have also been able to use our crystal structures as scaffolds to model the possible structural effects of missense mutations that have been identified in factor XIII-deficient patients.

Key words:

Factor XIII - transglutaminase - crystal structure - x-ray crystallography - catalytic triad

PDF (1670 kb)