Submitted September 24, 2007
Accepted December 3, 2007
The X-ray crystal structure of the fibrinolysis inhibitor 
2-antiplasmin
Ruby H.P. Law, Trifina Sofian, Wan-Ting Kan, Anita J. Horvath, Corinne R. Hitchen, Christopher G. Langendorf, Ashley M. Buckle, James C. Whisstock*, and Paul B. Coughlin
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
Australian Centre for Blood Diseases, Monash University, Prahran, Victoria, Australia
ARC Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria, Australia
* Corresponding author; email: james.whisstock{at}med.monash.edu.au.
The serpin 
2-antiplasmin (SERPINF2) is the principal inhibitor of plasmin and inhibits fibrinolysis. Accordingly, 2-antiplasmin deficiency in humans results in uncontrolled fibrinolysis and a bleeding disorder. 2-antiplasmin is an unusual serpin, in that it contains extensive N- and C-terminal sequences flanking the serpin domain. The N-terminal sequence is crosslinked to fibrin by factor XIIIa, whereas the C-terminal region mediates the initial interaction with plasmin. To understand how this may happen, we have determined the 2.65 Å X-ray crystal structure of an N-terminal truncated murine 2-antiplasmin. The structure reveals that part of the C-terminal sequence is tightly associated with the body of the serpin. This would be anticipated to position the flexible plasmin-binding portion of the C-terminus in close proximity to the serpin Reactive Centre Loop where it may template serpin / protease interactions.
