4ZOT

Crystal structure of BbKI, a disulfide-free plasma kallikrein inhibitor at 1.4 A resolution

Summary for 4ZOT

• Entry DOI: 10.2210/pdb4zot/pdb
• Descriptor: Kunitz-type serine protease inhibitor BbKI (2 entities in total)
• Functional Keywords: kallikrein inhibitor, kunitz-type kallikrein inhibitor, protein binding
• Biological source: Bauhinia bauhinioides
• Total number of polymer chains: 1
• Total formula weight: 18365.74

Authors

Shabalin, I.G.,Zhou, D.,Wlodawer, A.,Oliva, M.L.V. (deposition date: 2015-05-06, release date: 2015-05-20, Last modification date: 2023-09-27)

Primary citation

Zhou, D.,Hansen, D.,Shabalin, I.G.,Gustchina, A.,Vieira, D.F.,de Brito, M.V.,Araujo, A.P.,Oliva, M.L.,Wlodawer, A.
Structure of BbKI, a disulfide-free plasma kallikrein inhibitor.
Acta Crystallogr.,Sect.F, 71:1055-1062, 2015

PubMed Abstract: A serine protease inhibitor from Bauhinia bauhinioides (BbKI) belongs to the Kunitz family of plant inhibitors, which are common in plant seeds. BbKI does not contain any disulfides, unlike most other members of this family. It is a potent inhibitor of plasma kallikrein, in addition to other serine proteases, and thus exhibits antithrombotic activity. A high-resolution crystal structure of recombinantly expressed BbKI was determined (at 1.4 Å resolution) and was compared with the structures of other members of the family. Modeling of a complex of BbKI with plasma kallikrein indicates that changes in the local structure of the reactive loop that includes the specificity-determining Arg64 are necessary in order to explain the tight binding. An R64A mutant of BbKI was found to be a weaker inhibitor of plasma kallikrein, but was much more potent against plasmin, suggesting that this mutant may be useful for preventing the breakup of fibrin and maintaining clot stability, thus preventing excessive bleeding.

PubMed: 26249699
DOI: 10.1107/S2053230X15011127

Experimental method

X-RAY DIFFRACTION (1.4 Å)