The Three-dimensional Crystal Structure of Cholera Toxin

Zhang, Rongguang; Scott, David; Westbrook, Mary L.; Nance, S.; Spangler, Brenda D.; Shipley, G. Graham; Westbrook, Edwin M.

doi:10.1006/jmbi.1995.0456

Cited by 303 publications

(139 citation statements)

References 9 publications

(12 reference statements)

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“…This toxin is responsible for the severe diarrhea, causing deaths of hundreds of thousands of people in the developing world [1]. The cholera toxin is a heterohexameric protein consisting of one A-subunit and five B-subunits (AB 5 ) [2,3]. Each B-subunit contains 103 amino acid residues that are spread among two α-helices and ten β-strands [2,4,5].…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulation of Cholera Toxin A-1 Polypeptide

2016

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A molecular dynamics (MD) simulation study of the enzymatic portion of cholera toxin; cholera toxin A-1 polypeptide (CTA1) was performed at 283, 310 and 323 K. From total energy analysis it was observed that this toxin is stable thermodynamically and these outcomes were likewise confirmed by root mean square deviations (RMSD) investigations. The Cα root mean square fluctuation (RMSF) examinations revealed that there are a number of residues inside CTA1, which can be used as target for designing and synthesizing inhibitory drugs, in order to inactivate cholera toxin inside the human body. The fluctuations in the radius of gyration and hydrogen bonding in CTA1 proved that protein unfolding and refolding were normal routine phenomena in its structure at all temperatures. Solvent accessible surface area study identified the hydrophilic nature of the CTA1, and due to this property it can be a potential biological weapon. The structural identification (STRIDE) algorithm for proteins was successfully used to determine the partially disordered secondary structure of CTA1. On account of this partially disordered secondary structure, it can easily deceive the proteolytic enzymes of the endoplasmic reticulum of host cells.

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Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulation of Cholera Toxin A-1 Polypeptide

2016

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“…The 3D structures of several protein ADP-ribosyltransferases have been reported including chicken poly(ADP-ribose) polymerase (PARP)-1 (14), rat ART2.2 (15), mosquitocidal toxin from Bacillus sphaericus (16), diphtheria toxin (17), cholera toxin (18), domain III of Pseudomonas aeruginosa exotoxin A (19), iota-toxin from Clostridium perfringens (20), pertussis toxin (21), C2-toxin (22), and C3-toxin (23) from Clostridium botulinum.…”

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confidence: 99%

Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr

Baysarowich

Koteva

Hughes

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

157

195

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The rifamycin antibiotic rifampin is important for the treatment of tuberculosis and infections caused by multidrug-resistant Staphylococcus aureus. Recent iterations of the rifampin core structure have resulted in new drugs and drug candidates for the treatment of a much broader range of infectious diseases. This expanded use of rifamycin antibiotics has the potential to select for increased resistance. One poorly characterized mechanism of resistance is through Arr enzymes that catalyze ADP-ribosylation of rifamycins. We find that genes encoding predicted Arr enzymes are widely distributed in the genomes of pathogenic and nonpathogenic bacteria. Biochemical analysis of three representative Arr enzymes from environmental and pathogenic bacterial sources shows that these have equally efficient drug resistance capacity in vitro and in vivo. The 3D structure of one of these orthologues from Mycobacterium smegmatis was determined and reveals structural homology with ADP-ribosyltransferases important in eukaryotic biology, including poly(ADP-ribose) polymerases (PARPs) and bacterial toxins, despite no significant amino acid sequence homology with these proteins. This work highlights the extent of the rifamycin resistome in microbial genera with the potential to negatively impact the expanded use of this class of antibiotic.crystallography ͉ resistome ͉ rifampin ͉ ribosyltransferase

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“…V. cholerae expresses a number of virulence and colonization factors, including the coordinately expressed cholera toxin (CT) and the toxin coregulated pilus (TCP), to cause disease (2). The primary virulence factor CT, which is largely responsible for the symptoms of cholera, is a hexameric protein complex composed of five B subunits and a single A subunit (3)(4)(5). The B-subunit pentamer is responsible for binding the toxin to its receptor, GM1-ganglioside (5).…”

mentioning

confidence: 99%

Directed polar secretion of protease from single cells of Vibrio cholerae via the type II secretion pathway

Scott

Dossani

Sandkvist

2001

Proc. Natl. Acad. Sci. U.S.A.

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Bacteria have long been thought of as little more than sacks of homogeneously distributed enzymes. However, recent cytological studies indicate that bacteria are compartmentalized with proteins involved in processes such as cell division, motility, chemotaxis, and development located at distinct sites. We have used the green fluorescent protein as a reporter to determine the cellular distribution of the extracellular protein secretion (eps)-encoded type II secretion complex responsible for extracellular secretion of cholera toxin and hemagglutinin͞protease in Vibrio cholerae. Real-time monitoring of green fluorescent protein fused to EpsM in living cells indicated that, like the single polar flagellum, the Eps complex is located at the old pole after cell division. Eps-dependent protease secretion was also visualized in single cells by fluorescence microscopy by using intramolecularly quenched casein. This analysis demonstrated that active protease secretion is focused at the poles and colocalizes with the site of the polar Eps apparatus. These results suggest that the type II secretion complex is responsible for directed delivery of virulence factors during cholera pathogenesis.

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The Three-dimensional Crystal Structure of Cholera Toxin

Cited by 303 publications

References 9 publications

Molecular Dynamics Simulation of Cholera Toxin A-1 Polypeptide

Molecular Dynamics Simulation of Cholera Toxin A-1 Polypeptide

Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr

Directed polar secretion of protease from single cells of Vibrio cholerae via the type II secretion pathway

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