3UIR

Crystal structure of the plasmin-textilinin-1 complex

Summary for 3UIR

• Entry DOI: 10.2210/pdb3uir/pdb
• Related: 3BYB 3D65
• Descriptor: Plasmin light chain B, Textilinin-1, SULFATE ION, ... (4 entities in total)
• Functional Keywords: serine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00747 Q90WA1
• Total number of polymer chains: 4
• Total formula weight: 67781.28

Authors

Guddat, L.W.,Millers, E.K.,de jersey, J.,Lavin, M.F.,Masci, P.M. (deposition date: 2011-11-05, release date: 2012-12-26, Last modification date: 2024-11-13)

Primary citation

Millers, E.K.,Johnson, L.A.,Birrell, G.W.,Masci, P.P.,Lavin, M.F.,de Jersey, J.,Guddat, L.W.
The structure of human microplasmin in complex with textilinin-1, an aprotinin-like inhibitor from the Australian brown snake.
Plos One, 8:e54104-e54104, 2013

PubMed Abstract: Textilinin-1 is a Kunitz-type serine protease inhibitor from Australian brown snake venom. Its ability to potently and specifically inhibit human plasmin (K(i) = 0.44 nM) makes it a potential therapeutic drug as a systemic anti-bleeding agent. The crystal structures of the human microplasmin-textilinin-1 and the trypsin-textilinin-1 complexes have been determined to 2.78 Å and 1.64 Å resolution respectively, and show that textilinin-1 binds to trypsin in a canonical mode but to microplasmin in an atypical mode with the catalytic histidine of microplasmin rotated out of the active site. The space vacated by the histidine side-chain in this complex is partially occupied by a water molecule. In the structure of microplasminogen the χ(1) dihedral angle of the side-chain of the catalytic histidine is rotated by 67° from its "active" position in the catalytic triad, as exemplified by its location when microplasmin is bound to streptokinase. However, when textilinin-1 binds to microplasmin the χ(1) dihedral angle of this amino acid residue changes by -157° (i.e. in the opposite rotation direction compared to microplasminogen). The unusual mode of interaction between textilinin-1 and plasmin explains textilinin-1's selectivity for human plasmin over plasma kallikrein. This difference can be exploited in future drug design efforts.

PubMed: 23335990
DOI: 10.1371/journal.pone.0054104

Experimental method

X-RAY DIFFRACTION (2.777 Å)