Highly Selective and Tunable Protein Hydrolysis by a Polyoxometalate Complex in Surfactant Solutions: A Step toward the Development of Artificial Metalloproteases for Membrane Proteins

Annelies Sap; Laurens Vandebroek; Vincent Goovaerts; Erik Martens; Paul Proost; Tatjana N Parac-Vogt

doi:10.1021/acsomega.7b00168

Highly Selective and Tunable Protein Hydrolysis by a Polyoxometalate Complex in Surfactant Solutions: A Step toward the Development of Artificial Metalloproteases for Membrane Proteins

ACS Omega. 2017 May 31;2(5):2026-2033. doi: 10.1021/acsomega.7b00168. Epub 2017 May 11.

Authors

Annelies Sap¹, Laurens Vandebroek¹, Vincent Goovaerts¹, Erik Martens², Paul Proost², Tatjana N Parac-Vogt¹

Affiliations

¹ Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Box 2404, 3001 Leuven, Belgium.
² Department of Microbiology and Immunology, KU Leuven, Herestraat 49, Box 1042, 3000 Leuven, Belgium.

Abstract

This study represents the first example of protein hydrolysis at pH = 7.4 and 60 °C by a metal-substituted polyoxometalate (POM) in the presence of a zwitterionic surfactant. Edman degradation results show that in the presence of 0.5% w/v 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) detergent, a Zr(IV)-substituted Wells-Dawson-type POM, K₁₅H[Zr(α₂-P₂W₁₇O₆₁)₂]·25H₂O (Zr1-WD2), selectively hydrolyzes human serum albumin exclusively at peptide bonds involving Asp or Glu residues, which contain carboxyl groups in their side chains. The selectivity and extent of protein cleavage are tuned by the CHAPS surfactant by an unfolding mechanism that provides POM access to the hydrolyzed peptide bonds.