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Ames, Giovanna Ferro‐Luzzi; Nikaido, Kishiko; Wang, Iris Xiaoyan; Liu, Peiqi; Liu, Cheng E.; Hu, Calvin

doi:10.1023/a:1010797029183

Cited by 34 publications

(7 citation statements)

References 35 publications

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“…ATPase assay. ATPase activity of reconstituted transporter complexes was assayed in the presence or absence of 0.4 mg/ml HisJ with 1 mM L-histidine or LAO with L-arginine, as described previously (30,47).…”

Section: Methodsmentioning

confidence: 99%

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Evidence from Mutational Analysis for a Single Transmembrane Substrate Binding Site in the Histidine ATP-Binding Cassette Transporter of Salmonella enterica Serovar Typhimurium

2019

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The histidine ATP-binding cassette (ABC) transporter of Salmonella enterica serovar Typhimurium is among the best-studied type I ABC import systems. The transporter consists of two transmembrane subunits, HisQ and HisM, and a homodimer of the nucleotide-binding subunit, HisP. Substrates are delivered by two periplasmic solute binding proteins, HisJ and LAO, with preferences for histidine and for lysine, arginine, and ornithine, respectively. A homology model was built by using the arginine-bound crystal structure of the closely related Art(QN) 2 transporter of Thermoanaerobacter tengcongensis as the template. In the homodimeric Art(QN) 2 , one substrate molecule is bound to each of the ArtQ subunits, whereas the structural model and sequence alignments predict only one substrate molecule in contact with HisM. To address the question whether one or two binding sites exist in heterodimeric HisQM, we have studied the functional consequences of mutations by monitoring (i) the complementation of growth on D-histidine of auxotrophic tester strains, (ii) the growth of tester strains on arginine as a nitrogen source, and (iii) AT-Pase activity of purified variants in a lipid environment. Our results demonstrate that two negatively charged residues, namely, HisM-E166 and HisQ-D61, are indispensable for function. Furthermore, the complete reconstruction of an ArtQ-like binding site in HisQ resulted in an inactive transporter. Likewise, switching the positions of both negatively charged residues between HisQ and HisM caused transport-deficient phenotypes. Thus, we propose that one substrate molecule is primarily liganded by residues of HisM while HisQ-D61 forms a crucial salt bridge with the ␣-amino group of the substrate. IMPORTANCE Canonical ATP-binding cassette (ABC) importers are major players in the translocation of numerous nutrients, vitamins, and growth factors to the cytoplasm of prokaryotes. Moreover, some ABC importers have been identified as virulence factors in bacterial pathogenesis. Thus, a full understanding of their mode of action is considered a prerequisite, among others, for the development of novel antibacterial drugs. However, mainly owing to the lack of structural information, the knowledge of the chemical nature and number of substrate binding sites formed by the transmembrane subunits of ABC importers is scarce. Here, we provide evidence from mutational analyses that, in contrast to homologous homodimeric systems, the heterodimeric histidine transporter of Salmonella enterica serovar Typhimurium is liganding only one substrate molecule between its transmembrane subunits, HisM and HisQ. KEYWORDS ATP-binding cassette transporters, Salmonella enterica serovar Typhimurium, type I ABC importer, histidine transporter, mutational analysis, transmembrane substrate binding site Citation Heuveling J, Landmesser H, Schneider E. 2019. Evidence from mutational analysis for a single transmembrane substrate binding site in the histidine ATP-binding cassette transporter of Salmonella enterica serovar Typhimurium. J...

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Section: Methodsmentioning

confidence: 99%

“…However, transporters for positively charged amino acids exist in both homoand heterodimeric compositions. The best-studied heterodimeric system is the histidine transporter, HisQMP 2 , of Salmonella enterica serovar Typhimurium (2,(28)(29)(30)(31).…”

mentioning

confidence: 99%

Evidence from Mutational Analysis for a Single Transmembrane Substrate Binding Site in the Histidine ATP-Binding Cassette Transporter of Salmonella enterica Serovar Typhimurium

2019

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“…Histidine can enter Salmonella typhimurium by at least five uptake system ((12); Chapter XX on Amino Acid Utilization), including the high-affinity histidine periplasmic-binding-protein (HisJ-HisQ-HisM-HisP) system (Table 2). The histidine periplasmic-binding-protein permease has been studied extensively by G. F. Ames and coworkers (see references (15, 18, 79, 149, 168) and is one of the best characterized ABC ATP-dependent transport systems (see Chapter XX). The K m of the HisJ-HisQ-HisM-HisP permease for histidine is about 10 -8 M and the K d (histidine) of the HisJ periplasmic binding protein is about 0.1 μM, which means that its affinity for histidine is orders of magnitude greater than that of some of the other histidine transport systems (12); Chapter XX).…”

Section: Histidine Transportmentioning

confidence: 99%

Biosynthesis of Histidine

Winkler

Ramos‐Montañez²

2009

EcoSal Plus

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The biosynthesis of histidine in Escherichia coli and Salmonella typhimurium has been an important model system for the study of relationships between the flow of intermediates through a biosynthetic pathway and the control of the genes encoding the enzymes that catalyze the steps in a pathway. This article provides a comprehensive review of the histidine biosynthetic pathway and enzymes, including regulation of the flow of intermediates through the pathway and mechanisms that regulate the amounts of the histidine biosynthetic enzymes. In addition, this article reviews the structure and regulation of the histidine ( his ) biosynthetic operon, including transcript processing, Rho-factor-dependent “classical” polarity, and the current model of his operon attenuation control. Emphasis is placed on areas of recent progress. Notably, most of the enzymes that catalyze histidine biosynthesis have recently been crystallized, and their structures have been determined. Many of the histidine biosynthetic intermediates are unstable, and the histidine biosynthetic enzymes catalyze some chemically unusual reactions. Therefore, these studies have led to considerable mechanistic insight into the pathway itself and have provided deep biochemical understanding of several fundamental processes, such as feedback control, allosteric interactions, and metabolite channeling. Considerable recent progress has also been made on aspects of his operon regulation, including the mechanism of pp(p)Gpp stimulation of his operon transcription, the molecular basis for transcriptional pausing by RNA polymerase, and pathway evolution. The progress in these areas will continue as sophisticated new genomic, metabolomic, proteomic, and structural approaches converge in studies of the histidine biosynthetic pathway and mechanisms of control of his biosynthetic genes in other bacterial species.

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“…[4][5][6][7][8][9][10][11][12] However, the mechanism of conformational changes induced by the binding of ATP in wild type and mutant proteins, functions of important conserved residues and mechanism of ATP hydrolysis in ABC transporters still remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Theoretical Study on the ATP Hydrolysis Mechanism of HisP Protein, the ATP-Binding Subunit of ABC Transporter

et al. 2007

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ATP binding subunit is known as a subunit of ABC transporter, providing energy through the binding of ATP with the subunit and the subsequent hydrolysis reaction of the bound ATP. In this study, density functional theory (DFT) method was used to study the ATP hydrolysis reaction in HisP protein, an ATP binding subunit of Histidine permease HisQMP 2 , by considering the ATP binding site, especially thephosphate group, surrounding residues and water molecules. Based on DFT calculations, we proposed that ATP hydrolysis is initiated by the formation of Mg 2þ mediated coordinate complex followed by the nucleophilic attack of a single water molecule (Water437) on the -phosphate; the hydrolysis product ADP acts as a leaving group. The transition state structure was determined by an approximate saddle-point search.

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Untitled

Cited by 34 publications

References 35 publications

Evidence from Mutational Analysis for a Single Transmembrane Substrate Binding Site in the Histidine ATP-Binding Cassette Transporter of Salmonella enterica Serovar Typhimurium

Evidence from Mutational Analysis for a Single Transmembrane Substrate Binding Site in the Histidine ATP-Binding Cassette Transporter of Salmonella enterica Serovar Typhimurium

Biosynthesis of Histidine

Theoretical Study on the ATP Hydrolysis Mechanism of HisP Protein, the ATP-Binding Subunit of ABC Transporter

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