Guerra, Yasel, Valiente, Pedro A., Pons, Tirso, Berry, Colin ![]() |
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Abstract
Bi-functional inhibitors from the Kunitz-type soybean trypsin inhibitor (STI) family are glycosylated proteins able to inhibit serine and aspartic proteases. Here we report six crystal structures of the wild-type and a non-glycosylated mutant of the bifunctional inhibitor E3Ad obtained at different pH values and space groups. The crystal structures show that E3Ad adopts the typical β-trefoil fold of the STI family exhibiting some conformational changes due to pH variations and crystal packing. Despite the high sequence identity with a recently reported potato cathepsin D inhibitor (PDI), three-dimensional structures obtained in this work show a significant conformational change in the protease-binding loop proposed for aspartic protease inhibition. The E3Ad binding loop for serine protease inhibition is also proposed, based on structural similarity with a novel non-canonical conformation described for the double-headed inhibitor API-A from the Kunitz-type STI family. In addition, structural and sequence analyses suggest that bifunctional inhibitors of serine and aspartic proteases from the Kunitz-type STI family are more similar to double-headed inhibitor API-A than other inhibitors with a canonical protease-binding loop.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences |
Subjects: | Q Science > QH Natural history > QH301 Biology |
Uncontrolled Keywords: | aspartic protease inhibitors, Kunitz-type STI family inhibitors, bi-functional inhibitors, plant protease inhibitors, β-trefoil fold |
Publisher: | Elsevier |
ISSN: | 1047-8477 |
Date of First Compliant Deposit: | 4 May 2017 |
Date of Acceptance: | 18 June 2016 |
Last Modified: | 17 Nov 2024 00:00 |
URI: | https://orca.cardiff.ac.uk/id/eprint/95774 |
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