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Crystal Structures ...
Crystal Structures Exploring the Origins of the Broader Specificity of Escherichia coli Heat-Labile Enterotoxin Compared to Cholera Toxin.
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Holmner, Åsa (author)
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Mackenzie, Alasdair (author)
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Ökvist, M. (author)
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- Jansson, Lena, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Lebens, Michael, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Teneberg, Susann, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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Krengel, Ute, 1964 (author)
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(creator_code:org_t)
- Elsevier BV, 2011
- 2011
- English.
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In: Journal of molecular biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 406:3, s. 387-402
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http://dx.doi.org/10...
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https://doi.org/10.1...
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Abstract
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- Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are structurally and functionally related and share the same primary receptor, the GM1 ganglioside. Despite their extensive similarities, these two toxins exhibit distinct ligand specificities, with LT being more promiscuous than CT. Here, we have attempted to rationalize the broader binding specificity of LT and the subtle differences between the binding characteristics of LTs from human and porcine origins (mediated by their B subunit pentamers, hLTB and pLTB, respectively). The analysis is based on two crystal structures of pLTB in complexes with the pentasaccharide of its primary ligand, GM1, and with neolactotetraose, the carbohydrate determinant of a typical secondary ligand of LTs, respectively. Important molecular determinants underlying the different binding specificities of LTB and CTB are found to be contributed by Ser95, Tyr18 and Thr4 (or Ser4 of hLTB), which together prestabilize the binding site by positioning Lys91, Glu51 and the adjacent loop region (50-61) containing Ile58 for ligand binding. Glu7 and Ala1 may also play an important role. Many of these residues are closely connected with a recently identified second binding site, and there appears to be cross-talk between the two binding sites. Binding to N-acetyllactosamine-terminated receptors is further augmented by Arg13 (present in pLT and some hLT variants), as previously predicted.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Keyword
- importance of conformational entropy for molecular recognition
- bacterial toxins
- protein–carbohydrate interactions
- host–pathogen interactions
- X-ray crystal structure
- bacterial toxins; host–pathogen interactions; importance of conformational entropy for molecular recognition; protein–carbohydrate interactions; X-ray crystal structure
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Holmner, Åsa
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Mackenzie, Alasd ...
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Ökvist, M.
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Jansson, Lena, 1 ...
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Lebens, Michael, ...
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Teneberg, Susann ...
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show more...
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Krengel, Ute, 19 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Other Basic Medi ...
- Articles in the publication
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Journal of molec ...
- By the university
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Chalmers University of Technology
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University of Gothenburg