2EBF

Crystal structures reveal a thiol-protease like catalytic triad in the C-terminal region of Pasteurella multocida toxin

Summary for 2EBF

• Entry DOI: 10.2210/pdb2ebf/pdb
• Related: 2EBH 2EC5
• Related PRD ID: PRD_900006
• Descriptor: Dermonecrotic toxin, alpha-D-glucopyranose-(1-1)-alpha-D-glucopyranose, PHOSPHONATE, ... (4 entities in total)
• Functional Keywords: pasteurella multocida toxin, trojan horse-like fold, toxin
• Biological source: Pasteurella multocida
• Cellular location: Cytoplasm (Probable): P17452
• Total number of polymer chains: 1
• Total formula weight: 85062.18

Authors

Kitadokoro, K.,Horiguchi, Y.,Kamitani, S. (deposition date: 2007-02-08, release date: 2007-03-06, Last modification date: 2020-07-29)

Primary citation

Kitadokoro, K.,Kamitani, S.,Miyazawa, M.,Hanajima-Ozawa, M.,Fukui, A.,Miyake, M.,Horiguchi, Y.
Crystal structures reveal a thiol protease-like catalytic triad in the C-terminal region of Pasteurella multocida toxin
Proc.Natl.Acad.Sci.Usa, 104:5139-5144, 2007

PubMed Abstract: Pasteurella multocida toxin (PMT), one of the virulence factors produced by the bacteria, exerts its toxicity by up-regulating various signaling cascades downstream of the heterotrimeric GTPases Gq and G12/13 in an unknown fashion. Here, we present the crystal structure of the C-terminal region (residues 575-1,285) of PMT, which carries an intracellularly active moiety. The overall structure of C-terminal region of PMT displays a Trojan horse-like shape, composed of three domains with a "feet"-,"body"-, and "head"-type arrangement, which were designated C1, C2, and C3 from the N to the C terminus, respectively. The C1 domain, showing marked similarity in steric structure to the N-terminal domain of Clostridium difficile toxin B, was found to lead the toxin molecule to the plasma membrane. The C3 domain possesses the Cys-His-Asp catalytic triad that is organized only when the Cys is released from a disulfide bond. The steric alignment of the triad corresponded well to that of papain or other enzymes carrying Cys-His-Asp. PMT toxicities on target cells were completely abrogated when one of the amino acids constituting the triad was mutated. Our results indicate that PMT is an enzyme toxin carrying the cysteine protease-like catalytic triad dependent on the redox state and functions on the cytoplasmic face of the plasma membrane of target cells.

PubMed: 17360394
DOI: 10.1073/pnas.0608197104

Experimental method

X-RAY DIFFRACTION (1.9 Å)