Centerin [SERPINA9/GCET1 (germinal centre B-cell-expressed transcript 1)] is a
serpin (
serine protease inhibitor) whose expression is restricted to germinal centre B-cells and lymphoid
malignancies with germinal centre B-cell maturation. Expression of
centerin, together with bcl-6 and GCET2, constitutes a germinal centre B-cell signature, which is associated with a good prognosis in diffuse large
B-cell lymphomas, but the molecular basis for this remains to be elucidated. We report here the cloning, expression and molecular characterization of bacterial recombinant
centerin. Biophysical studies demonstrated that
centerin was able to undergo the 'stressed to relaxed' conformational change which is an absolute requirement for
protease inhibitory activity. Kinetic analysis showed that
centerin rapidly inhibited the
serine protease trypsin (k(a)=1.9x10(5) M(-1) x s(-1)) and also demonstrated measurable inhibition of
thrombin (k(a)=1.17x10(3) M(-1) x s(-1)) and
plasmin (k(a)=1.92x10(3) M(-1) x s(-1)).
Centerin also bound
DNA and
unfractionated heparin, although there was no functionally significant impact on the rate of inhibition. These results suggest that
centerin is likely to function in vivo in the germinal centre as an efficient inhibitor of a
trypsin-like
protease.