Linked Life Data

15049684

Source:http://linkedlifedata.com/resource/pubmed/id/15049684

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2004-3-30
pubmed:databankReference
pubmed:abstractText
Cholera toxin (CT) is a heterohexameric bacterial protein toxin belonging to a larger family of A/B ADP-ribosylating toxins. Each of these toxins undergoes limited proteolysis and/or disulfide bond reduction to form the enzymatically active toxic fragment. Nicking and reduction render both CT and the closely related heat-labile enterotoxin from Escherichia coli (LT) unstable in solution, thus far preventing a full structural understanding of the conformational changes resulting from toxin activation. We present the first structural glimpse of an active CT in structures from three crystal forms of a single-site A-subunit CT variant, Y30S, which requires no activational modifications for full activity. We also redetermined the structure of the wild-type, proenzyme CT from two crystal forms, both of which exhibit (i) better geometry and (ii) a different A2 "tail" conformation than the previously determined structure [Zhang et al. (1995) J. Mol. Biol. 251, 563-573]. Differences between wild-type CT and active CTY30S are observed in A-subunit loop regions that had been previously implicated in activation by analysis of the structure of an LT A-subunit R7K variant [van den Akker et al. (1995) Biochemistry 34, 10996-11004]. The 25-36 activation loop is disordered in CTY30S, while the 47-56 active site loop displays varying degrees of order in the three CTY30S structures, suggesting that disorder in the activation loop predisposes the active site loop to a greater degree of flexibility than that found in unactivated wild-type CT. On the basis of these six new views of the CT holotoxin, we propose a model for how the activational modifications experienced by wild-type CT are communicated to the active site.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3772-82
pubmed:dateRevised
2008-8-20
pubmed:meshHeading
pubmed-meshheading:15049684-Bacterial Toxins, pubmed-meshheading:15049684-Binding Sites, pubmed-meshheading:15049684-Cholera Toxin, pubmed-meshheading:15049684-Crystallization, pubmed-meshheading:15049684-Crystallography, X-Ray, pubmed-meshheading:15049684-Enterotoxins, pubmed-meshheading:15049684-Escherichia coli Proteins, pubmed-meshheading:15049684-Galactose, pubmed-meshheading:15049684-Mutagenesis, Site-Directed, pubmed-meshheading:15049684-Peptide Fragments, pubmed-meshheading:15049684-Protein Binding, pubmed-meshheading:15049684-Protein Conformation, pubmed-meshheading:15049684-Protein Structure, Secondary, pubmed-meshheading:15049684-Protein Subunits, pubmed-meshheading:15049684-Serine, pubmed-meshheading:15049684-Structure-Activity Relationship, pubmed-meshheading:15049684-Tyrosine
pubmed:year
2004
pubmed:articleTitle
Crystal structures of an intrinsically active cholera toxin mutant yield insight into the toxin activation mechanism.
pubmed:affiliation
Department of Chemistry and Biomolecular Structure Center, University of Washington, Seattle, Washington 98195, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't