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Small-Molecule Supp...
Small-Molecule Suppression of Misfolding of Mutated Human Carbonic Anhydrase II Linked to Marble Brain Disease
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- Almstedt, Karin (author)
- Linköpings universitet,Biokemi,Tekniska högskolan
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- Rafstedt, Therese (author)
- Linköpings universitet,Institutionen för fysik, kemi och biologi,Tekniska högskolan
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- Supuran, Claudiu T (author)
- University of Florence
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- Carlsson, Uno (author)
- Linköpings universitet,Biokemi,Tekniska högskolan
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- Hammarström, Per (author)
- Linköpings universitet,Biokemi,Tekniska högskolan
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(creator_code:org_t)
- 2009-05-20
- 2009
- English.
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In: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 48:23, s. 5358-5364
- Related links:
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http://urn.kb.se/res...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Carbonic anhydrase II deficiency syndrome or Marble brain disease (MBD) is caused by autosomal recessive mutations in the human carbonic anhydrase II (HCA II) gene. Here we report a small-molecule stabilization study of the exceptionally destabilized HCA II mutant H107Y employing inhibitors based on p-aminobenzoyisulfonamide compounds and 1,3,4-thiadiazolylsulfonamides as well as amino acid activators. Protein stability assays showed a significant stabilization by the aromatic sulfonamide inhibitors when present at 10 mu M concentration, providing shifts of the midpoint of thermal denaturation between 10 degrees C and 16 degrees C and increasing the free energies of denaturation 0.5-3.0 kcal/mol as deduced from GuHCl denaturation. This study could be used as a starting point for the design of small-molecule folding modulators and possibly autoactivatable molecules for suppression of misfolding of destabilized HCA II mutants.
Keyword
- NATURAL SCIENCES
- NATURVETENSKAP
Publication and Content Type
- ref (subject category)
- art (subject category)
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