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The structure of recombinant (Hoover et al. Biochemistry, 1993; 32:10936-10944)
plasminogen (PG) kringle 1 (K1) has been determined and refined at 2.48 A
resolution to a crystallographic R value of 0.159. In addition, 71 water
molecules and two chloride ions have been located. The folding of PGK1 is very
similar to that of PGK4. The lysine/fibrin binding site, however, differs from
that of both PGK4 and tissue-type PG activator (t-PA) K2 at the cationic centre.
Although PGK1 can potentially have a doubly charged cationic centre utilizing
Arg34 and Arg71, the side chain of Arg34 is outside of Arg71 in a solvent region
and its guanidino group is flexibly disordered. Moreover, site specific
mutagenesis studies show unequivocally that Arg34 can be changed to glutamine
without affecting the binding ability of PGK1. Thus, PGK1 only has Arg71 at the
cationic site, PGK4 has Lys35/Arg71 and t-PAK2 has only Lys33. The cationic site
differences may result in subtle responses in the binding affinities of the
kringles. The two chloride ions are located in the lysine binding site and
effectively compensate the positive charges of the region. They also appear to
be involved intermolecularly in a complex way in the crystal structure. Such
intermolecular anionic interactions are also found in PGK4 and t-PAK2.
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