1bth | pdb_00001bth
STRUCTURE OF THROMBIN COMPLEXED WITH BOVINE PANCREATIC TRYPSIN INHIBITOR
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Overview
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.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1BTH is a Protein complex structure of sequences from Bos taurus. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
The thrombin E192Q-BPTI complex reveals gross structural rearrangements: implications for the interaction with antithrombin and thrombomodulin., van de Locht A, Bode W, Huber R, Le Bonniec BF, Stone SR, Esmon CT, Stubbs MT, EMBO J. 1997 Jun 2;16(11):2977-84. PMID:9214615
Page seeded by OCA on Fri Feb 15 15:33:24 2008
