Small Molecule-Induced Allosteric Activation of the Vibrio cholerae RTX Cysteine Protease Domain-Reference-Cited by-同舟云学术

Small Molecule-Induced Allosteric Activation of the Vibrio cholerae RTX Cysteine Protease Domain

Published:2008-10-10 Issue:5899 Volume:322 Page:265-268
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Lupardus Patrick J.¹²³,Shen Aimee¹²³,Bogyo Matthew¹²³,Garcia K. Christopher¹²³

Affiliation:

1. Department of Molecular and Cellular Physiology and Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

2. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

3. Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Abstract

Vibrio cholerae RTX (repeats in toxin) is an actin-disrupting toxin that is autoprocessed by an internal cysteine protease domain (CPD). The RTX CPD is efficiently activated by the eukaryote-specific small molecule inositol hexakisphosphate (InsP 6 ), and we present the 2.1 angstrom structure of the RTX CPD in complex with InsP 6 . InsP 6 binds to a conserved basic cleft that is distant from the protease active site. Biochemical and kinetic analyses of CPD mutants indicate that InsP 6 binding induces an allosteric switch that leads to the autoprocessing and intracellular release of toxin-effector domains.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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