Structure of the lysine-fibrin binding subsite of human plasminogen kringle 4.
Human plasminogen kringle 4, which crystallizes in the orthorhombic system a = 32.15(2), b = 49.01(2), c = 49.04(3) A, space group P2(1)2(1)2(1), four molecules per unit cell, protein volume fraction 0.62, has been determined at 1.9 A resolution. The structure was solved by rotation-translation methods using the structure of bovine prothrombin kringle 1 as a model and it has been refined at 1.9 A resolution to an R-value of 0.142. The root mean square (rms) deviation between the main-chain atoms of the two kringles is about 0.5 A while that between 31 conserved side chains is a surprisingly large 1.2 A. The structure of the lysine binding subsite of fibrin binding of kringle 4 is approximated well by prothrombin kringle 1 but with some notable exceptions. The latter transform the site from a non-binding kringle to one which recognizes lysine and other omega-amino-carboxylic acids. The binding site of the observed kringle 4 structure is also compared with one that was modelled from the structure of kringle 1 of prothrombin fragment 1 and NMR observations. Arginine residues of the binding site of a neighbouring molecule make ion pairs with aspartic acid residues in the binding site of another molecule in the kringle 4 structure.
Mulichak
A M
AM
Department of Chemistry, Michigan State University, East Lansing 48824.
Tulinsky
A
A
D000595:Amino Acid Sequence; D001665:Binding Sites; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D008239:Lysine; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D010446:Peptide Fragments; D005337:Fibrin; D010958:Plasminogen; D008239:Lysine