Functional and solution structure studies of amino sugar deacetylase and deaminase enzymes from <i>Staphylococcus aureus</i>

Davies, James S.; Coombes, David; Horne, Christopher R; Pearce, F. Grant; Friemann, Rosmarie; North, Rachel A.; Dobson, Renwick C. J.

doi:10.1002/1873-3468.13289

Cited by 23 publications

(30 citation statements)

References 41 publications

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“…As shown in Figure 3A Figure 3B). The binding motif at this region, 8 GxGxxG 13 confers cofactor specificity for NAD(H) over NADP(H). 56 Specifically, the cofactor was recognized by the side chains of residues F12, D33, N36, N70, H73, K91, W160, and K161, through an interaction that was mediated by an ordered water molecule ( Figure S5).…”

Section: Cofactor Bindingmentioning

confidence: 99%

“…5 In addition, the catabolism of sialic acids yield precursors for peptidoglycan biosynthesis, such as N-acetylglucosamine. 7,8 Lastly, some bacteria can decorate their cell surfaces with host-derived sialic acids to camouflage themselves against the host innate immune system. 1,9 Given the accessibility of sialic acids in mucus rich environments, their utilization offers pathogenic bacteria and commensals, such as Escherichia coli, a competitive advantage to colonize and persist within the human host.…”

Section: Introductionmentioning

confidence: 99%

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On the structure and function of Escherichia coli YjhC: An oxidoreductase involved in bacterial sialic acid metabolism

et al. 2019

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Human pathogenic and commensal bacteria have evolved the ability to scavenge host‐derived sialic acids and subsequently degrade them as a source of nutrition. Expression of the Escherichia coli yjhBC operon is controlled by the repressor protein nanR, which regulates the core machinery responsible for the import and catabolic processing of sialic acid. The role of the yjhBC encoded proteins is not known—here, we demonstrate that the enzyme YjhC is an oxidoreductase/dehydrogenase involved in bacterial sialic acid degradation. First, we demonstrate in vivo using knockout experiments that YjhC is broadly involved in carbohydrate metabolism, including that of N‐acetyl‐d‐glucosamine, N‐acetyl‐d‐galactosamine and N‐acetylneuraminic acid. Differential scanning fluorimetry demonstrates that YjhC binds N‐acetylneuraminic acid and its lactone variant, along with NAD(H), which is consistent with its role as an oxidoreductase. Next, we solved the crystal structure of YjhC in complex with the NAD(H) cofactor to 1.35 Å resolution. The protein fold belongs to the Gfo/Idh/MocA protein family. The dimeric assembly observed in the crystal form is confirmed through solution studies. Ensemble refinement reveals a flexible loop region that may play a key role during catalysis, providing essential contacts to stabilize the substrate—a unique feature to YjhC among closely related structures. Guided by the structure, in silico docking experiments support the binding of sialic acid and several common derivatives in the binding pocket, which has an overall positive charge distribution. Taken together, our results verify the role of YjhC as a bona fide oxidoreductase/dehydrogenase and provide the first evidence to support its involvement in sialic acid metabolism.

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Section: Cofactor Bindingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

On the structure and function of Escherichia coli YjhC: An oxidoreductase involved in bacterial sialic acid metabolism

et al. 2019

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“…Moreover in [19] authors utilize Fourier transform infrared spectroscopy to investigate kinetics of a series of five DNA sequences to clarify the commonly observed physical processes. As a result of our study, it was shown that SMCs in the composition of drugs undergo hysteresis phenomena, exhibiting long-period conformational mobility, which probably should be taken into account when the drug is tested in vitro [8,12]. Hysteresis phenomena in water-lactose SMCs illustrated by the results of two spectral methods of analysis are most likely associated with the influence of environmental factors such as variations in relative humidity, temperature, background variations in the level of natural radioactivity, including the flux of thermal neutrons [20,21], which can be a source of energy for conformational rearrangements [22,23].…”

Section: Discussionmentioning

confidence: 76%

“…The observed kinetic transitions suggest the existence of a free energy barrier between the states of the supramolecular structure. The process can be compared with the kinetic trapping phenomenon, well studied, and described for protein molecules, associated with conformational differences between the long-lived transitional and stable final states [7,8].…”

Section: Fig 1: the Formation Of A Water-lactose Complex (Smc) And Rmentioning

confidence: 99%

Slow Quasikinetic Changes in Water-Lactose Complexes During Storage

Морозова¹,

Koldina²,

Максимова³

et al. 2021

Int J App Pharm

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Objective: To investigate kinetic changes in the spectral characteristics by Fourier Transform Infrared spectroscopy (FTIR) of water-lactose complexes (SMC), derived during the manufacturing process of the drug, containing release-active forms of antibodies. Methods: lactose monohydrate substance, saturated with release-active forms of affinity-purified polyclonal rabbit antibodies to recombinant human interferon-gamma (RA forms of Abs); tablets produced from this substance by direct compression after the addition of excipients (microcrystalline cellulose, magnesium stearate). Powdered and tableted placebo samples saturated with technologically processed water or phosphate-buffered saline, as well as with intact ethanol were used as control. Kinetic changes in SMC were studied using an Agilent Cary 630 FTIR spectrophotometer with a diamond ATR accessory (Agilent Technologies, USA). We used the method of X-ray fluorescence spectroscopy (EDX-7000 Shimadzu energy dispersive X-ray fluorescence spectrometer) to track changes in the fluorescence signal at certain wavelengths. The range of measured elements–11Na-92U. Results: Control of some technological characteristics of the obtained active substance (moisture, flowability) and dosage form (mean mass, disintegration rate) was used as indirect indicators of quality, but they did not allow reliably distinguishing intact lactose from the saturated one. Long-period oscillations on FTIR spectra were characteristic for all types of samples; oscillations occur at approximately two-week intervals; S/N indices were more stable for samples of RA forms of Abs than for placebo samples. On some days, the substance saturated with RA forms of Abs significantly differed from the intact lactose powder. The kinetics of the X-ray fluorescence intensity at certain wavelengths indicates the possibility of a periodic cooperative trigger transition of the system. Reversible conformational transitions are observed for powders on the 30th and 130th days (Kα 3.313 keV). For tablets at Kα 3.313 keV and Kα 1.740 keV small changes were visualized on those days (100–110th day) when hysteresis phenomena were recorded in the IR spectra of these samples. Conclusion: As a result, the evidence for a long-period dramatic conformational mobility of the water-lactose complex was obtained. Based on the data on the semiannual kinetics of IR spectra, a universal criterion for the identity of lactose powder saturated with RA forms of Abs was obtained. Also, it was confirmed that the lactose conformation state was changed by saturation with RA forms of Abs.

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“…These TRAPs transport sialic acids, a family of nine-carbon amino sugars, the most common of which is N- acetylneuraminic acid ( North et al, 2018 ). The focus on these systems is due to the growing interest in the role of sialic acid as an important nutrient source for pathogenic bacteria in vivo ( North et al, 2016 ; North et al, 2018 ; Wahlgren et al, 2018 ; Davies et al, 2019 ; Coombes et al, 2020 ; Horne et al, 2021 ). Electrochemical studies have been used to characterise the transport of sialic acid through the H. influenzae SiaPQM system ( Mulligan et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Selective Nutrient Transport in Bacteria: Multicomponent Transporter Systems Reign Supreme

Davies

Currie

Wright

et al. 2021

Front. Mol. Biosci.

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Multicomponent transporters are used by bacteria to transport a wide range of nutrients. These systems use a substrate-binding protein to bind the nutrient with high affinity and then deliver it to a membrane-bound transporter for uptake. Nutrient uptake pathways are linked to the colonisation potential and pathogenicity of bacteria in humans and may be candidates for antimicrobial targeting. Here we review current research into bacterial multicomponent transport systems, with an emphasis on the interaction at the membrane, as well as new perspectives on the role of lipids and higher oligomers in these complex systems.

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Functional and solution structure studies of amino sugar deacetylase and deaminase enzymes from Staphylococcus aureus

Cited by 23 publications

References 41 publications

On the structure and function of Escherichia coli YjhC: An oxidoreductase involved in bacterial sialic acid metabolism

On the structure and function of Escherichia coli YjhC: An oxidoreductase involved in bacterial sialic acid metabolism

Slow Quasikinetic Changes in Water-Lactose Complexes During Storage

Selective Nutrient Transport in Bacteria: Multicomponent Transporter Systems Reign Supreme

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