1TPK

CRYSTAL STRUCTURE OF THE KRINGLE-2 DOMAIN OF TISSUE PLASMINOGEN ACTIVATOR AT 2.4-ANGSTROMS RESOLUTION

Summary for 1TPK

• Entry DOI: 10.2210/pdb1tpk/pdb
• Descriptor: TISSUE PLASMINOGEN ACTIVATOR, CHLORIDE ION (3 entities in total)
• Functional Keywords: plasminogen activator
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space: P00750
• Total number of polymer chains: 3
• Total formula weight: 29067.67

Authors

De vos, A.M.,Ultsch, M.H.,Kelley, R.F.,Padmanabhan, K.,Tulinsky, A.,Westbrook, M.L.,Kossiakoff, A.A. (deposition date: 1991-09-24, release date: 1992-07-15, Last modification date: 2024-10-30)

Primary citation

de Vos, A.M.,Ultsch, M.H.,Kelley, R.F.,Padmanabhan, K.,Tulinsky, A.,Westbrook, M.L.,Kossiakoff, A.A.
Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4-A resolution.
Biochemistry, 31:270-279, 1992

PubMed Abstract: The crystal structure of the kringle 2 domain of tissue plasminogen activator was determined and refined at a resolution of 2.43 A. The overall fold of the molecule is similar to that of prothrombin kringle 1 and plasminogen kringle 4; however, there are differences in the lysine binding pocket, and two looping regions, which include insertions in kringle 2, take on very different conformations. Based on a comparison of the overall structural homology between kringle 2 and kringle 4, a new sequence alignment for kringle domains is proposed that results in a division of kringle domains into two groups, consistent with their proposed evolutionary relation. The crystal structure shows a strong interaction between a lysine residue of one molecule and the lysine/fibrin binding pocket of a noncrystallographically related neighbor. This interaction represents a good model of a bound protein ligand and is the first such ligand that has been observed in a kringle binding pocket. The structure shows an intricate network of interactions both among the binding pocket residues and between binding pocket residues and the lysine ligand. A lysine side chain is identified as the positively charged group positioned to interact with the carboxylate of lysine and lysine analogue ligands. In addition, a chloride ion is located in the kringle-kringle interface and contributes to the observed interaction between kringle molecules.

PubMed: 1310033
DOI: 10.1021/bi00116a037

Experimental method

X-RAY DIFFRACTION (2.4 Å)