Journal Article

FZJ-2021-02624

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Glutamine synthetase as a central element in hepatic glutamine and ammonia metabolism: novel aspects

Frieg, B.FZJ* ; Görg, B. ; Gohlke, H. (Corresponding author)FZJ* ; Häussinger, D. (Corresponding author)

2021
de Gruyter Berlin [u.a.]

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Please use a persistent id in citations: http://hdl.handle.net/2128/28510  doi:10.1515/hsz-2021-0166

Abstract: Glutamine synthetase (GS) in the liver is expressed in a small perivenous, highly specializedhepatocyte population and is essential for the maintenance of low, non‐toxic ammonia levelsin the organism. However, GS activity can be impaired by tyrosine nitration of the enzyme inresponse to oxidative/nitrosative stress in a pH‐sensitive way. The underlying molecularmechanism as investigated by combined molecular simulations and in vitro experimentsindicates that tyrosine nitration can lead to a fully reversible and pH‐sensitive regulation ofprotein function. This approach was also used to understand the functional consequences ofseveral recently described point mutations of human GS with clinical relevance and to suggestan approach to restore impaired GS activity.

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Contributing Institute(s):

1. Bioinformatik (IBG-4)
2. John von Neumann - Institut für Computing (NIC)
3. Jülich Supercomputing Center (JSC)
4. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. 2171 - Biological and environmental resources for sustainable use (POF4-217) (POF4-217)
3. 2172 - Utilization of renewable carbon and energy sources and engineering of ecosystem functions (POF4-217) (POF4-217)
4. 511 - Computational Science and Mathematical Methods (POF3-511) (POF3-511)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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