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Structure and function studies of factor XIIIa by x-ray crystallography
V C Yee1, I Le Trong, P D Bishop
1Biochemistry Department, University of Washington, Seattle 98195-7350, USA.
Seminars in Thrombosis and Hemostasis
|January 1, 1996
Summary
Structural insights into factor XIII A subunit were revealed through X-ray crystallography, detailing its active site and ion-binding residues. This research aids understanding of transglutaminase function and factor XIII deficiency mutations.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Medicine
Background:
- Factor XIII (FXIII) is a crucial enzyme in blood coagulation, primarily involved in stabilizing fibrin clots.
- Understanding the three-dimensional structure of the FXIII A subunit is essential for elucidating its transglutaminase activity and the molecular basis of FXIII deficiency.
Purpose of the Study:
- To determine the high-resolution three-dimensional structures of various forms of the factor XIII A subunit.
- To identify key residues involved in catalysis and ion binding.
- To provide a structural basis for understanding missense mutations associated with factor XIII deficiency.
Main Methods:
- Single crystal X-ray diffraction was employed to determine the structures.
- Crystallographic data were analyzed to identify conserved residues and active site features.
- Structural models were used to predict the effects of identified missense mutations.
Main Results:
- The first detailed structural view of the factor XIII A subunit was obtained.
- A conserved catalytic triad (Cys314-His373-Asp396) in the active site was identified.
- Conserved acidic residues (Asp438, Glu485, Glu490) involved in calcium and strontium ion binding were revealed.
Conclusions:
- The determined structures offer critical insights into transglutaminase function of the factor XIII A subunit.
- The structural information can guide the understanding of FXIII-related bleeding disorders.
- The study provides a framework for modeling the impact of genetic mutations on protein structure and function.