Aarhus Universitets segl

English

Du er her: AU » Om AU » Organisation » Variant of the Thermomyces lanuginosus lipase with improv...

Om AU

Variant of the Thermomyces lanuginosus lipase with improved kinetic stability: a candidate for enzyme replacement therapy

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Standard

Variant of the Thermomyces lanuginosus lipase with improved kinetic stability: a candidate for enzyme replacement therapy. / Wang, Huabing; Hagedorn, J; Svendsen, A et al.
I: Biophysical Chemistry, Bind 172, 02.2013, s. 43-52.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Harvard

Wang, H, Hagedorn, J, Svendsen, A, Borch, K & Otzen, D 2013, 'Variant of the Thermomyces lanuginosus lipase with improved kinetic stability: a candidate for enzyme replacement therapy', Biophysical Chemistry, bind 172, s. 43-52. https://doi.org/10.1016/j.bpc.2012.12.003

APA

Wang, H., Hagedorn, J., Svendsen, A., Borch, K., & Otzen, D. (2013). Variant of the Thermomyces lanuginosus lipase with improved kinetic stability: a candidate for enzyme replacement therapy. Biophysical Chemistry, 172, 43-52. https://doi.org/10.1016/j.bpc.2012.12.003

CBE

Wang H, Hagedorn J, Svendsen A, Borch K, Otzen D. 2013. Variant of the Thermomyces lanuginosus lipase with improved kinetic stability: a candidate for enzyme replacement therapy. Biophysical Chemistry. 172:43-52. https://doi.org/10.1016/j.bpc.2012.12.003

MLA

Wang, Huabing et al. "Variant of the Thermomyces lanuginosus lipase with improved kinetic stability: a candidate for enzyme replacement therapy". Biophysical Chemistry. 2013, 172. 43-52. https://doi.org/10.1016/j.bpc.2012.12.003

Vancouver

Wang H, Hagedorn J, Svendsen A, Borch K, Otzen D. Variant of the Thermomyces lanuginosus lipase with improved kinetic stability: a candidate for enzyme replacement therapy. Biophysical Chemistry. 2013 feb.;172:43-52. doi: 10.1016/j.bpc.2012.12.003

Author

Wang, Huabing ; Hagedorn, J ; Svendsen, A et al. / Variant of the Thermomyces lanuginosus lipase with improved kinetic stability : a candidate for enzyme replacement therapy. I: Biophysical Chemistry. 2013 ; Bind 172. s. 43-52.

Bibtex

@article{2ebc9e6cd727453fb79edab6e2b2b713,
title = "Variant of the Thermomyces lanuginosus lipase with improved kinetic stability: a candidate for enzyme replacement therapy",
abstract = "Lipases with high kinetic stability and enzymatic efficiency in the human gastro-intestinal tract may help against exocrine pancreatic insufficiency. Here we mimic gastric conditions to study how bile salts and pH affect the stability and activity of Thermomyces lanuginosus lipase (TlL) and its stabler variant StL using spectroscopy, calorimetry and gel electrophoresis. Both enzymes resist trypsin digestion with and without bile salts. Bile salts activate native TlL and StL equally well, bind weakly to denatured TlL and StL at lower pH and precipitate native TlL and StL at pH 4. StL refolds more efficiently than TlL from gastric pH in bile salts, regaining activity when refolding from pH as low as 1.8 and above while TlL cannot go below pH 2.6. StL also unfolds 10-40 fold more slowly in the denaturant guanidinium chloride and the anionic surfactant SDS. We ascribe StL's superior performance to general alterations in its electrostatic potential which makes it more acid-resistant. These superior properties make StL a good candidate for pancreatic enzyme replacement therapy.",
keywords = "Ascomycota, Bile Acids and Salts, Calorimetry, Differential Scanning, Enzyme Replacement Therapy, Exocrine Pancreatic Insufficiency, Gastrointestinal Agents, Humans, Hydrogen-Ion Concentration, Kinetics, Lipase, Mutant Proteins, Mutation, Protein Folding",
author = "Huabing Wang and J Hagedorn and A Svendsen and K Borch and Daniel Otzen",
note = "Copyright {\textcopyright} 2012 Elsevier B.V. All rights reserved.",
year = "2013",
month = feb,
doi = "10.1016/j.bpc.2012.12.003",
language = "English",
volume = "172",
pages = "43--52",
journal = "Biophysical Chemistry",
issn = "0301-4622",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Variant of the Thermomyces lanuginosus lipase with improved kinetic stability

T2 - a candidate for enzyme replacement therapy

AU - Wang, Huabing

AU - Hagedorn, J

AU - Svendsen, A

AU - Borch, K

AU - Otzen, Daniel

N1 - Copyright © 2012 Elsevier B.V. All rights reserved.

PY - 2013/2

Y1 - 2013/2

N2 - Lipases with high kinetic stability and enzymatic efficiency in the human gastro-intestinal tract may help against exocrine pancreatic insufficiency. Here we mimic gastric conditions to study how bile salts and pH affect the stability and activity of Thermomyces lanuginosus lipase (TlL) and its stabler variant StL using spectroscopy, calorimetry and gel electrophoresis. Both enzymes resist trypsin digestion with and without bile salts. Bile salts activate native TlL and StL equally well, bind weakly to denatured TlL and StL at lower pH and precipitate native TlL and StL at pH 4. StL refolds more efficiently than TlL from gastric pH in bile salts, regaining activity when refolding from pH as low as 1.8 and above while TlL cannot go below pH 2.6. StL also unfolds 10-40 fold more slowly in the denaturant guanidinium chloride and the anionic surfactant SDS. We ascribe StL's superior performance to general alterations in its electrostatic potential which makes it more acid-resistant. These superior properties make StL a good candidate for pancreatic enzyme replacement therapy.

AB - Lipases with high kinetic stability and enzymatic efficiency in the human gastro-intestinal tract may help against exocrine pancreatic insufficiency. Here we mimic gastric conditions to study how bile salts and pH affect the stability and activity of Thermomyces lanuginosus lipase (TlL) and its stabler variant StL using spectroscopy, calorimetry and gel electrophoresis. Both enzymes resist trypsin digestion with and without bile salts. Bile salts activate native TlL and StL equally well, bind weakly to denatured TlL and StL at lower pH and precipitate native TlL and StL at pH 4. StL refolds more efficiently than TlL from gastric pH in bile salts, regaining activity when refolding from pH as low as 1.8 and above while TlL cannot go below pH 2.6. StL also unfolds 10-40 fold more slowly in the denaturant guanidinium chloride and the anionic surfactant SDS. We ascribe StL's superior performance to general alterations in its electrostatic potential which makes it more acid-resistant. These superior properties make StL a good candidate for pancreatic enzyme replacement therapy.

KW - Ascomycota

KW - Bile Acids and Salts

KW - Calorimetry, Differential Scanning

KW - Enzyme Replacement Therapy

KW - Exocrine Pancreatic Insufficiency

KW - Gastrointestinal Agents

KW - Humans

KW - Hydrogen-Ion Concentration

KW - Kinetics

KW - Lipase

KW - Mutant Proteins

KW - Mutation

KW - Protein Folding

U2 - 10.1016/j.bpc.2012.12.003

DO - 10.1016/j.bpc.2012.12.003

M3 - Journal article

C2 - 23357413

VL - 172

SP - 43

EP - 52

JO - Biophysical Chemistry

JF - Biophysical Chemistry

SN - 0301-4622

ER -