Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease.

In the United States non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, affecting an estimated 80 to 100 million people. It occurs in every age group, but predominantly in people with risk factors such as obesity and type 2 diabetes. NAFLD is marked by fat ac...

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Autores principales:	Michael W Moran, Elizabeth P Ramirez, James D Zook, Alicia M Saarinen, Bobby Baravati, Matthew R Goode, Vasiliki Laloudakis, Emily K Kaschner, Tien L Olson, Felicia M Craciunescu, Debra T Hansen, Jun Liu, Petra Fromme
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df709f94f5d2437182ca1909b6b7e4f4
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spelling	oai:doaj.org-article:df709f94f5d2437182ca1909b6b7e4f42021-12-02T20:05:04ZBiophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease.1932-620310.1371/journal.pone.0249164https://doaj.org/article/df709f94f5d2437182ca1909b6b7e4f42021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0249164https://doaj.org/toc/1932-6203In the United States non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, affecting an estimated 80 to 100 million people. It occurs in every age group, but predominantly in people with risk factors such as obesity and type 2 diabetes. NAFLD is marked by fat accumulation in the liver leading to liver inflammation, which may lead to scarring and irreversible damage progressing to cirrhosis and liver failure. In animal models, genetic ablation of the protein G0S2 leads to alleviation of liver damage and insulin resistance in high fat diets. The research presented in this paper aims to aid in rational based drug design for the treatment of NAFLD by providing a pathway for a solution state NMR structure of G0S2. Here we describe the expression of G0S2 in an E. coli system from two different constructs, both of which are confirmed to be functionally active based on the ability to inhibit the activity of Adipose Triglyceride Lipase. In one of the constructs, preliminary NMR spectroscopy measurements show dominant alpha-helical characteristics as well as resonance assignments on the N-terminus of G0S2, allowing for further NMR work with this protein. Additionally, the characterization of G0S2 oligomers are outlined for both constructs, suggesting that G0S2 may defensively exist in a multimeric state to protect and potentially stabilize the small 104 amino acid protein within the cell. This information presented on the structure of G0S2 will further guide future development in the therapy for NAFLD.Michael W MoranElizabeth P RamirezJames D ZookAlicia M SaarinenBobby BaravatiMatthew R GoodeVasiliki LaloudakisEmily K KaschnerTien L OlsonFelicia M CraciunescuDebra T HansenJun LiuPetra FrommePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0249164 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael W Moran Elizabeth P Ramirez James D Zook Alicia M Saarinen Bobby Baravati Matthew R Goode Vasiliki Laloudakis Emily K Kaschner Tien L Olson Felicia M Craciunescu Debra T Hansen Jun Liu Petra Fromme Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease.
description	In the United States non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, affecting an estimated 80 to 100 million people. It occurs in every age group, but predominantly in people with risk factors such as obesity and type 2 diabetes. NAFLD is marked by fat accumulation in the liver leading to liver inflammation, which may lead to scarring and irreversible damage progressing to cirrhosis and liver failure. In animal models, genetic ablation of the protein G0S2 leads to alleviation of liver damage and insulin resistance in high fat diets. The research presented in this paper aims to aid in rational based drug design for the treatment of NAFLD by providing a pathway for a solution state NMR structure of G0S2. Here we describe the expression of G0S2 in an E. coli system from two different constructs, both of which are confirmed to be functionally active based on the ability to inhibit the activity of Adipose Triglyceride Lipase. In one of the constructs, preliminary NMR spectroscopy measurements show dominant alpha-helical characteristics as well as resonance assignments on the N-terminus of G0S2, allowing for further NMR work with this protein. Additionally, the characterization of G0S2 oligomers are outlined for both constructs, suggesting that G0S2 may defensively exist in a multimeric state to protect and potentially stabilize the small 104 amino acid protein within the cell. This information presented on the structure of G0S2 will further guide future development in the therapy for NAFLD.
format	article
author	Michael W Moran Elizabeth P Ramirez James D Zook Alicia M Saarinen Bobby Baravati Matthew R Goode Vasiliki Laloudakis Emily K Kaschner Tien L Olson Felicia M Craciunescu Debra T Hansen Jun Liu Petra Fromme
author_facet	Michael W Moran Elizabeth P Ramirez James D Zook Alicia M Saarinen Bobby Baravati Matthew R Goode Vasiliki Laloudakis Emily K Kaschner Tien L Olson Felicia M Craciunescu Debra T Hansen Jun Liu Petra Fromme
author_sort	Michael W Moran
title	Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease.
title_short	Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease.
title_full	Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease.
title_fullStr	Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease.
title_full_unstemmed	Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease.
title_sort	biophysical characterization and a roadmap towards the nmr solution structure of g0s2, a key enzyme in non-alcoholic fatty liver disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/df709f94f5d2437182ca1909b6b7e4f4
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Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease.

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