Kringle‐2 domain of the tissue‐type plasminogen activator

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Abstract
A recombinant 90‐residue polypeptide fragment containing the three‐loop kringle‐2 domain of human tissue‐type plasminogen activator (t‐PA) has been studied by two‐dimensional 1H‐NMR spectroscopy at 500 MHz. Complete sequence‐specific resonance assignments were derived. Overall, the kringle exhibits a compact, folded conformation with more than 50% of the residues in irregular structures. Elements of secondary structure were identified from sequential, medium‐ and long‐range dipolar (Overhauser) interproton interactions. These identifications were corroborated by analysis of spin‐spin scalar 3JαN splittings and identification of backbone amide NH protons exhibiting retarded 1H/2H exchange in 2H2O. Three antiparallel β‐sheets and six tight turns were located. In addition, one short α‐helical region was found in the Ser43‐Ala44 ‐Gln44a‐Ala44b‐Leu44c‐Gly45 segment; this region contains three‐residue insertions unique to the t‐PA and urokinase kringles. Although the secondary structure of the t‐PA kringle 2 in solution is in overall agreement with that observed in the crystallographic structure of the prothrombin kringle 1 [Tulinsky, A., Park, C. H. & Skrzypczak‐Jankun, E. (1988) J. Mol. Biol. 202, 885–901], the α‐helical segment and other details of the secondary structure differ somewhat from the prothrombin homolog.

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