Work

Molecular Architecture of the Inositol Phosphatase Siw14

Year: 2018

Type: article

Abstract: Siw14 is a recently discovered inositol phosphatase implicated in suppressing prion propagation in Saccharomyces cerevisiae. In this paper, we used hybrid structural methods to decipher Siw14 molecular architecture. We found the protein exists in solution as an elongated monomer that is ∼140 Å in length, containing an acidic N-terminal domain and a basic C-terminal dual-specificity phosphatase (DSP) domain, structurally similar to the glycogen phosphatase laforin. The two domains are connected by a protease susceptible linker and do not interact in vitro. The crystal structure of Siw14-DSP reveals a highly basic phosphate-binding loop and an ∼10 Å deep substrate-binding crevice that evolved to dephosphorylate pyro-phosphate moieties. A pseudoatomic model of the full-length phosphatase generated from solution, crystallographic, biochemical, and modeling data sheds light on the interesting zwitterionic nature of Siw14, which we hypothesized may play a role in discriminating negatively charged inositol phosphates.

Source: Biochemistry

DOI: 10.1021/acs.biochem.8b01044

Authors: Tyler J. Florio, Ravi K. Lokareddy, Richard E. Gillilan, Gino Cingolani

Institutions: Thomas Jefferson University, Cornell University, Cornell High Energy Synchrotron Source, Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Research Council

Language: English

Topic: Enzyme Structure and Function

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

Open Access status: green