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Synaptotagmin Bindi...
Synaptotagmin Binding to Botulinum Neurotoxins
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- Martínez-Carranza, Markel, 1992- (författare)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik
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- Blasco, Pilar (författare)
- Stockholm University,Stockholms universitet,Institutionen för organisk kemi
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- Gustafsson, Robert (författare)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik
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- Dong, Min (författare)
- Harvard Medical School,Boston Children's Hospital
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- Berntsson, Ronnie Per-Arne (författare)
- Umeå University,Umeå universitet,Institutionen för medicinsk kemi och biofysik,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)
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- Widmalm, Göran (författare)
- Stockholm University,Stockholms universitet,Institutionen för organisk kemi
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- Stenmark, Pål (författare)
- Stockholm University,Lunds universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Lund University, Sweden,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Strukturell biokemi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Structural Biochemistry,Lund University Research Groups
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(creator_code:org_t)
- 2019-12-06
- 2020
- Engelska.
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 59:4, s. 491-498
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http://su.diva-porta...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Botulinum neurotoxins (BoNTs) are exceptionally toxic proteins that cause paralysis but are also extensively used as treatment for various medical conditions. Most BoNTs bind two receptors on neuronal cells, namely, a ganglioside and a protein receptor. Differences in the sequence between the protein receptors from different species can impact the binding affinity and toxicity of the BoNTs. Here we have investigated how BoNT/B, /DC, and /G, all three toxins that utilize synaptotagmin I and II (Syt-I and Syt-II, respectively) as their protein receptors, bind to Syt-I and -II of mouse/rat, bovine, and human origin by isothermal titration calorimetry analysis. BoNT/G had the highest affinity for human Syt-I, and BoNT/DC had the highest affinity for bovine Syt-II. As expected, BoNT/B, /DC, and /G showed very low levels of binding to human Syt-II. Furthermore, we carried out saturation transfer difference (STD) and STD-TOCSY NMR experiments that revealed the region of the Syt peptide in direct contact with BoNT/G, which demonstrate that BoNT/G recognizes the Syt peptide in a model similar to that in the established BoNT/B-Syt-II complex. Our analyses also revealed that regions outside the Syt peptide’s toxin-binding region are important for the helicity of the peptide and, therefore, the binding affinity.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Nyckelord
- Biochemistry
- biokemi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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