Clostridium botulinum

Clostridium botulinum

Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...

 C3 exoenzyme is a toxin

Toxin

A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

 that causes the ADP-ribosylate of Rho-like proteins. Many bacterial toxins nucleotide-binding modify by ADP-ribosylation

ADP-ribosylation

ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis.-ADP-ribosylation enzymes:...

 proteins involved in essential cell functions.

The molecular basis of the action of these enzymes consists in binding of nicotinamide adenine dinucleotide

Nicotinamide adenine dinucleotide

Nicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...

 (NAD), splitting NAD into its ADP-ribose and nicotinamide

Nicotinamide

Nicotinamide, also known as niacinamide and nicotinic acid amide, is the amide of nicotinic acid . Nicotinamide is a water-soluble vitamin and is part of the vitamin B group...

 components, and transfering the ADP-ribose moiety to a specific residue on to a protein substrate, often of eukaryotic origin. All the toxins of this family share a highly conserved glutamate, which is the catalytic residue critical for the NAD-glycohydrolase activity. ADP-ribosyltransferase toxins have distinct substrate specificities and variable pathophysiological properties and can be subdivided into four subfamilies: diphtheria

Diphtheria

Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity...

-like toxins, cholera

Cholera

Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...

-like toxins, binary toxins and C3-like exoenzymes.

C3-like exoenzymes unlike other ADP-ribosyltransferase toxins do not require a specific cell-surface binding translocation component for cell entry. Their specificity is for the small GTP-binding proteins RhoA

RHOA

Ras homolog gene family, member A is a small GTPase protein known to regulate the actin cytoskeleton in the formation of stress fibers. In humans, it is encoded by the gene RHOA....

, RhoB

RHOB

Ras homolog gene family, member B, also known as RHOB, is a protein which in humans is encoded by the RHOB gene.RHOB is a member of the Rho GTP-binding protein family.-Interactions:...

, and RhoC

RhoC

RhoC is a small signaling G protein , and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC. -Mechanism and function:...

, which are ADP-ribosylated on an asparagine

Asparagine

Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...

residue.