Dataset Information

Acetylation Coordinates the Crosstalk between Carbon Metabolism and Ammonium Assimilation

ABSTRACT: Enteric bacteria use up to 15% of their cellular energy for ammonium assimilation via glutamine synthetase (GS)/glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH), in response to low or high ammonium availability. However, the sensory mechanisms for effective and appropriate coordination between carbon metabolism and ammonium assimilation are not fully elucidated. Here, we report that, in Salmonella, carbon metabolism coordinates the activities of GS/GDH via functional reversible protein lysine acetylation. Glucose simultaneously promotes acetyltransferase Pat-mediated acetylation on Lys164 and Lys353 of GS to activate the adenylylated-GS by inducing its conformation change, while on Lys128 of GDH to inactivate the enzyme by impeding its catalytic center, respectively, which are reversed by deacetylase CobB-mediated deacetylation. Molecular dynamic (MD) simulations indicated that the acetylation activation of GS activity was adenylylation-dependent. Acetylation and deacetylation occur within minutes of ‘glucose shock’ to promptly adapt to ammonium/carbon variation and finely balance glutamine/glutamate synthesis. Acetylation can rehabilitate the growth tardiness of Salmonella mutant with chromosomal mimetic mutation of adenylylated-GS and thus help its survival in mice. Thus, glucose-driven acetylation integrates the signals of assimilation and carbon metabolism for proper growth control.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Salmonella Typhimurium (strain Lt2 / Sgsc1412 / Atcc 700720)

SUBMITTER: Qijun Wang

LAB HEAD: Qijun Wang

PROVIDER: PXD039658 | Pride | 2023-06-21

REPOSITORIES: Pride

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Publications

Acetylation coordinates the crosstalk between carbon metabolism and ammonium assimilation in Salmonella enterica.

Sun Yunwei Y Zhang Yuebin Y Zhao Tingting T Luan Yi Y Wang Ying Y Yang Chen C Shen Bo B Huang Xi X Li Guohui G Zhao Shimin S Zhao Guo-Ping GP Wang Qijun Q

The EMBO journal 20230515 13

Enteric bacteria use up to 15% of their cellular energy for ammonium assimilation via glutamine synthetase (GS)/glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH) in response to varying ammonium availability. However, the sensory mechanisms for effective and appropriate coordination between carbon metabolism and ammonium assimilation have not been fully elucidated. Here, we report that in Salmonella enterica, carbon metabolism coordinates the activities of GS/GDH via functionally rever ...[more]

PMID: 37183585

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Project description:This a model from the article: The multifarious short-term regulation of ammonium assimilation of Escherichia coli: dissection using an in silico replica. Bruggeman FJ, Boogerd FC, Westerhoff HV. FEBS J. 2005 Apr;272(8):1965-85. 15819889 , Abstract: Ammonium assimilation in Escherichia coli is regulated through multiple mechanisms (metabolic, signal transduction leading to covalent modification, transcription, and translation), which (in-)directly affect the activities of its two ammonium-assimilating enzymes, i.e. glutamine synthetase (GS) and glutamate dehydrogenase (GDH). Much is known about the kinetic properties of the components of the regulatory network that these enzymes are part of, but the ways in which, and the extents to which the network leads to subtle and quasi-intelligent regulation are unappreciated. To determine whether our present knowledge of the interactions between and the kinetic properties of the components of this network is complete - to the extent that when integrated in a kinetic model it suffices to calculate observed physiological behaviour - we now construct a kinetic model of this network, based on all of the kinetic data on the components that is available in the literature. We use this model to analyse regulation of ammonium assimilation at various carbon statuses for cells that have adapted to low and high ammonium concentrations. We show how a sudden increase in ammonium availability brings about a rapid redirection of the ammonium assimilation flux from GS/glutamate synthase (GOGAT) to GDH. The extent of redistribution depends on the nitrogen and carbon status of the cell. We develop a method to quantify the relative importance of the various regulators in the network. We find the importance is shared among regulators. We confirm that the adenylylation state of GS is the major regulator but that a total of 40% of the regulation is mediated by ADP (22%), glutamate (10%), glutamine (7%) and ATP (1%). The total steady-state ammonium assimilation flux is remarkably robust against changes in the ammonium concentration, but the fluxes through GS and GDH are completely nonrobust. Gene expression of GOGAT above a threshold value makes expression of GS under ammonium-limited conditions, and of GDH under glucose-limited conditions, sufficient for ammonium assimilation. This version of the model originates from JWS online . The original model can be retrieved here . This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Dataset Information

Acetylation Coordinates the Crosstalk between Carbon Metabolism and Ammonium Assimilation

Publications

Acetylation coordinates the crosstalk between carbon metabolism and ammonium assimilation in Salmonella enterica.

Similar Datasets

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