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

Journal Article · Tue May 19 00:00:00 EDT 2009 · Science 322:265,2008

OSTI ID:953100

Lupardus, P J; Shen, A; Bogyo, M; Garcia, K C

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{sub 6}), and we present the 2.1 angstrom structure of the RTX CPD in complex with InsP{sub 6}. InsP{sub 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{sub 6} binding induces an allosteric switch that leads to the autoprocessing and intracellular release of toxin-effector domains.

• Research Organization: SLAC National Accelerator Lab., Menlo Park, CA (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC02-76SF00515
• OSTI ID: 953100
• Report Number(s): SLAC-REPRINT-2009-184; SCEHDK; TRN: US200914%%196
• Journal Information: Science 322:265,2008, Vol. 322; ISSN 0193-4511
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CYSTEINE
INOSITOL
BIOCHEMICAL REACTION KINETICS
MUTANTS
TOXINS
CHEMICAL ACTIVATION
PHOSPHATES
Other
OTHER