5FZU

CRYSTAL STRUCTURE OF N19D POTATO STI-KUNITZ BI-FUNCTIONAL INHIBITOR OF SERINE AND ASPARTIC PROTEASES IN SPACE GROUP P4322 AND PH 7.2

Summary for 5FZU

• Entry DOI: 10.2210/pdb5fzu/pdb
• Related: 5FZY 5FZZ 5G00
• Descriptor: KTI-A PROTEIN (2 entities in total)
• Functional Keywords: hydrolase, proteases, protease inhibitor, bi-functional protease inhibitor, hydrolase inhibitor, kunitz-type inhibitor
• Biological source: SOLANUM TUBEROSUM (POTATO)
• Total number of polymer chains: 1
• Total formula weight: 20527.49

Authors

Guerra, Y.,Rudino-Pinero, E. (deposition date: 2016-03-15, release date: 2016-07-06, Last modification date: 2024-10-23)

Primary citation

Guerra, Y.,Valiente, P.A.,Pons, T.,Berry, C.,Rudino-Pinera, E.
Structures of a bi-functional Kunitz-type STI family inhibitor of serine and aspartic proteases: Could the aspartic protease inhibition have evolved from a canonical serine protease-binding loop?
J. Struct. Biol., 195:259-271, 2016

PubMed 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.

PubMed: 27329566
DOI: 10.1016/j.jsb.2016.06.014

Experimental method

X-RAY DIFFRACTION (2.43 Å)