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80 a.a.
_CL
Key reference
Blood Coagul Fibrinolysis 5:157-166 (1994) PubMed id: 8054447
The structure of recombinant plasminogen kringle 1 and the fibrin binding site. T.P.Wu, K.P.Padmanabhan, A.Tulinsky. ABSTRACT
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.
Literature references that cite this PDB file's key reference
PubMed id Reference
14717962 J.H.Geiger, and S.E.Cnudde (2004).
What the structure of angiostatin may tell us about its mechanism of action.J Thromb Haemost, 2, 23-34.
12646571 S.C.Wu, F.J.Castellino, and S.L.Wong (2003).
A fast-acting, modular-structured staphylokinase fusion with Kringle-1 from human plasminogen as the fibrin-targeting domain offers improved clot lysis efficacy.J Biol Chem, 278, 18199-18206.
11928826 E.Anglés-Cano, and G.Rojas (2002).
Apolipoprotein(a): structure-function relationship at the lysine-binding site and plasminogen activator cleavage site.Biol Chem, 383, 93-99.
11928808 M.Gehrmann, K.Briknarová, L.Bányai, L.Patthy, and M.Llinás (2002).
The col-1 module of human matrix metalloproteinase-2 (MMP-2): structural/functional relatedness between gelatin-binding fibronectin type II modules and lysine-binding kringle domains.Biol Chem, 383, 137-148.
PDB code: 1ks0
11297431 J.A.Kornblatt, I.Rajotte, and F.Heitz (2001).
Reaction of canine plasminogen with 6-aminohexanoate: a thermodynamic study combining fluorescence, circular dichroism, and isothermal titration calorimetry.Biochemistry, 40, 3639-3647.
11369850 Q.Ye, M.N.Rahman, M.L.Koschinsky, and Z.Jia (2001).
High-resolution crystal structure of apolipoprotein(a) kringle IV type 7: insights into ligand binding.Protein Sci, 10, 1124-1129.
PDB code: 1i71
8910613 Y.Cao, R.W.Ji, D.Davidson, J.Schaller, D.Marti, S.Söhndel, S.G.McCance, M.S.O'Reilly, M.Llinás, and J.Folkman (1996).
Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells.J Biol Chem, 271, 29461-29467. The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.
