1BTH

STRUCTURE OF THROMBIN COMPLEXED WITH BOVINE PANCREATIC TRYPSIN INHIBITOR

Summary for 1BTH

• Entry DOI: 10.2210/pdb1bth/pdb
• Descriptor: THROMBIN, BOVINE PANCREATIC TRYPSIN INHIBITOR, ... (4 entities in total)
• Functional Keywords: thrombin inhibitor, serine proteinase kunitz-like inhibitor, (serine protease/inhibitor), complex (serine protease-inhibitor) complex, complex (serine protease/inhibitor)
• Biological source: Bos taurus (cattle); More
• Cellular location: Secreted, extracellular space: P00734 P00734; Secreted: P00974
• Total number of polymer chains: 6
• Total formula weight: 80866.73

Authors

Van De Locht, A.,Bode, W.,Stubbs, M.T. (deposition date: 1996-12-03, release date: 1997-12-24, Last modification date: 2021-11-03)

Primary citation

van de Locht, A.,Bode, W.,Huber, R.,Le Bonniec, B.F.,Stone, S.R.,Esmon, C.T.,Stubbs, M.T.
The thrombin E192Q-BPTI complex reveals gross structural rearrangements: implications for the interaction with antithrombin and thrombomodulin.
EMBO J., 16:2977-2984, 1997

PubMed Abstract: Previous crystal structures of thrombin indicate that the 60-insertion loop is a rigid moiety that partially occludes the active site, suggesting that this structural feature plays a decisive role in restricting thrombin's specificity. This restricted specificity is typified by the experimental observation that thrombin is not inhibited by micromolar concentrations of basic pancreatic trypsin inhibitor (BPTI). Surprisingly, a single atom mutation in thrombin (E192Q) results in a 10(-8) M affinity for BPTI. The crystal structure of human thrombin mutant E192Q has been solved in complex with BPTI at 2.3 A resolution. Binding of the Kunitz inhibitor is accompanied by gross structural rearrangements in thrombin. In particular, thrombin's 60-loop is found in a significantly different conformation. Concomitant reorganization of other surface loops that surround the active site, i.e. the 37-loop, the 148-loop and the 99-loop, is observed. Thrombin can therefore undergo major structural reorganization upon strong ligand binding. Implications for the interaction of thrombin with antithrombin and thrombomodulin are discussed.

PubMed: 9214615
DOI: 10.1093/emboj/16.11.2977

Experimental method

X-RAY DIFFRACTION (2.3 Å)