Crystal structures of the complex of a kallikrein inhibitor from Bauhinia bauhinioides with trypsin and modeling of kallikrein complexes

Li, Mi; Srp, Jaroslav; Gustchina, Alla; Dauter, Zbigniew; Mares, Michael; Wlodawer, Alexander

doi:10.1107/S2059798318016492

Crystal structures of the complex of a kallikrein inhibitor from Bauhinia bauhinioides with trypsin and modeling of kallikrein complexes

Journal Article · Tue Jan 01 04:00:00 EST 2019 · Acta Crystallographica. Section D. Structural Biology

DOI:https://doi.org/10.1107/S2059798318016492· OSTI ID:1506508

Li, Mi; ; Gustchina, Alla; Dauter, Zbigniew; Mares, Michael; Wlodawer, Alexander

Structures of a recombinant Kunitz-type serine protease inhibitor from Bauhinia bauhinioides (BbKI) complexed with bovine trypsin were determined in two crystal forms. The crystal structure with the L55R mutant of BbKI was determined in space group P6₄at 1.94 Å resolution and that with native BbKI in the monoclinic space group P2₁at 3.95 Å resolution. The asymmetric unit of the latter crystals contained 44 independent complexes, thus representing one of the largest numbers of independent objects deposited in the Protein Data Bank. Additionally, the structure of the complex with native BbKI was determined at 2.0 Å resolution from P6₄crystals isomorphous to those of the mutant. Since BbKI has previously been found to be a potent inhibitor of the trypsin-like plasma kallikrein, it was also tested against several tissue kallikreins. It was found that BbKI is a potent inhibitor of human tissue kallikrein 4 (KLK4) and the chymotrypsin-like human tissue kallikrein 7 (KLK7). Structures of BbKI complexed with the catalytic domain of human plasma kallikrein were modeled, as well as those with KLK4 and KLK7, and the structures were analyzed in order to identify the interactions that are responsible for inhibitory potency.

Research Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: NIH

OSTI ID:: 1506508

Journal Information:: Acta Crystallographica. Section D. Structural Biology, Journal Name: Acta Crystallographica. Section D. Structural Biology Journal Issue: 1 Vol. 75; ISSN 2059-7983; ISSN ACSDAD

Publisher:: IUCr

Country of Publication:: United States

Language:: ENGLISH

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