1HQ0

CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF E.COLI CYTOTOXIC NECROTIZING FACTOR TYPE 1

Summary for 1HQ0

• Entry DOI: 10.2210/pdb1hq0/pdb
• Related: 1HZG
• Descriptor: CYTOTOXIC NECROTIZING FACTOR 1, PHOSPHATE ION (3 entities in total)
• Functional Keywords: beta sandwich, rho deamidase, rho transglutaminase, toxin
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 32943.35

Authors

Buetow, L.,Flatau, G.,Chiu, K.,Boquet, P.,Ghosh, P. (deposition date: 2000-12-13, release date: 2001-07-04, Last modification date: 2024-02-07)

Primary citation

Buetow, L.,Flatau, G.,Chiu, K.,Boquet, P.,Ghosh, P.
Structure of the Rho-activating domain of Escherichia coli cytotoxic necrotizing factor 1.
Nat.Struct.Biol., 8:584-588, 2001

PubMed Abstract: Certain uropathogenic and neonatal meningitis-causing strains of Escherichia coli express a 114 kDa protein toxin called cytotoxic necrotizing factor 1 (CNF1). The toxin causes alteration of the host cell actin cytoskeleton and promotes bacterial invasion of blood-brain barrier endothelial cells. CNF1 belongs to a unique group of large cytotoxins that cause constitutive activation of Rho guanosine triphosphatases (GTPases), which are key regulators of the actin cytoskeleton. This group also includes E. coli cytotoxic necrotizing factor 2 (CNF2, 114 kDa) and dermonecrotic toxins (DNT, 159 kDa) of Bordetella spp. with related sequences occurring in Yersinia spp. Here we show that the catalytic region of CNF1 exhibits a novel protein fold as determined by its 1.83 A resolution crystal structure. The structure reveals that CNF1 has a Cys-His-main chain oxygen catalytic triad reminiscent of enzymes belonging to the catalytic triad superfamily. The position of the catalytic Cys residue at the base of a deep pocket restricts access to potential substrates and helps explain the high specificity of this and related toxins.

PubMed: 11427886
DOI: 10.1038/89610

Experimental method

X-RAY DIFFRACTION (1.83 Å)