Bacterial Heme-Based Sensors of Nitric Oxide

Williams, Dominique E; Nisbett, Lisa-Marie; Bacon, Bezalel; Boon, Elizabeth M.

doi:10.1089/ars.2017.7235

Cited by 22 publications

(37 citation statements)

References 113 publications

(210 reference statements)

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“… 32 As is the case for Af GcHK, gas binding to the distorted 5cHS Fe(II) heme alleviates heme distortion in these sensors, leading to conformational changes in the heme-bound sensor domain and subsequent changes in intra- and/or intermolecular interactions with partner proteins and downstream signal transduction. 32 …”

Section: Discussionmentioning

confidence: 98%

Characterization of a Cobalt-Substituted Globin-Coupled Oxygen Sensor Histidine Kinase from Anaeromyxobacter sp. Fw109-5: Insights into Catalytic Regulation by Its Heme Coordination Structure

2021

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Heme-based gas sensors are an emerging class of heme proteins. Af GcHK, a globin-coupled histidine kinase from Anaeromyxobacter sp. Fw109-5, is an oxygen sensor enzyme in which oxygen binding to Fe(II) heme in the globin sensor domain substantially enhances its autophosphorylation activity. Here, we reconstituted Af GcHK with cobalt protoporphyrin IX (Co- Af GcHK) in place of heme (Fe- Af GcHK) and characterized the spectral and catalytic properties of the full-length proteins. Spectroscopic analyses indicated that Co(III) and Co(II)-O 2 complexes were in a 6-coordinated low-spin state in Co- Af GcHK, like Fe(III) and Fe(II)-O 2 complexes of Fe- Af GcHK. Although both Fe(II) and Co(II) complexes were in a 5-coordinated state, Fe(II) and Co(II) complexes were in high-spin and low-spin states, respectively. The autophosphorylation activity of Co(III) and Co(II)-O 2 complexes of Co- Af GcHK was fully active, whereas that of the Co(II) complex was moderately active. This contrasts with Fe- Af GcHK, where Fe(III) and Fe(II)-O 2 complexes were fully active and the Fe(II) complex was inactive. Collectively, activity data and coordination structures of Fe- Af GcHK and Co- Af GcHK indicate that all fully active forms were in a 6-coordinated low-spin state, whereas the inactive form was in a 5-coordinated high-spin state. The 5-coordinated low-spin complex was moderately active—a novel finding of this study. These results suggest that the catalytic activity of Af GcHK is regulated by its heme coordination structure, especially the spin state of its heme iron. Our study presents the first successful preparation and characterization of a cobalt-substituted globin-coupled oxygen sensor enzyme and may lead to a better understanding of the molecular mechanisms of catalytic regulation in this family.

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Section: Discussionmentioning

confidence: 98%

Characterization of a Cobalt-Substituted Globin-Coupled Oxygen Sensor Histidine Kinase from Anaeromyxobacter sp. Fw109-5: Insights into Catalytic Regulation by Its Heme Coordination Structure

2021

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“…These include enzymes for their formation and detoxification and novel biological activities such as the lowing effect of nitrite on blood pressure [22,160]. In addition, nitrite and NO as signal molecules at very low concentrations are perceived by completely different sensing systems, through which they are linked to different biological processes [22,161]. Moreover, in recent years, nitrite has been gradually rediscovered as a beneficial molecule, either endogenously formed or therapeutically added [162,163].…”

Section: Hcos Are Primary Targets Of Nitrite But Not No In Vivomentioning

confidence: 99%

Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide

Chen

Xie

Huang

et al. 2022

IJMS

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Nitrite and nitric oxide (NO), two active and critical nitrogen oxides linking nitrate to dinitrogen gas in the broad nitrogen biogeochemical cycle, are capable of interacting with redox-sensitive proteins. The interactions of both with heme-copper oxidases (HCOs) serve as the foundation not only for the enzymatic interconversion of nitrogen oxides but also for the inhibitory activity. From extensive studies, we now know that NO interacts with HCOs in a rapid and reversible manner, either competing with oxygen or not. During interconversion, a partially reduced heme/copper center reduces the nitrite ion, producing NO with the heme serving as the reductant and the cupric ion providing a Lewis acid interaction with nitrite. The interaction may lead to the formation of either a relatively stable nitrosyl-derivative of the enzyme reduced or a more labile nitrite-derivative of the enzyme oxidized through two different pathways, resulting in enzyme inhibition. Although nitrite and NO show similar biochemical properties, a growing body of evidence suggests that they are largely treated as distinct molecules by bacterial cells. NO seemingly interacts with all hemoproteins indiscriminately, whereas nitrite shows high specificity to HCOs. Moreover, as biologically active molecules and signal molecules, nitrite and NO directly affect the activity of different enzymes and are perceived by completely different sensing systems, respectively, through which they are linked to different biological processes. Further attempts to reconcile this apparent contradiction could open up possible avenues for the application of these nitrogen oxides in a variety of fields, the pharmaceutical industry in particular.

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“…Without ANR, the NO-responsive second-tier regulator, DNR, is incapable of activating downstream nar , nir , nor , and nos genes ( Schreiber et al, 2007 ). Elegant recent work by Boon and colleagues have illuminated previously unrecognized NO binding proteins ( Hossain and Boon, 2017 ; Bacon et al, 2018 ; Williams et al, 2018 ; Williams and Boon, 2019 ). NosP, an NO-sensing protein, was discovered by Boon and colleagues as a critical protein involved in the dispersal of mature PA biofilms ( Hossain and Boon, 2017 ).…”

Section: How Does Pa Sense and Combat No?mentioning

confidence: 99%

“…NosP, an NO-sensing protein, was discovered by Boon and colleagues as a critical protein involved in the dispersal of mature PA biofilms ( Hossain and Boon, 2017 ). NosP was actually a protein that was anticipated to exist, for the majority of bacteria NO sensing protein are of the H-NOX variety ( Williams et al, 2018 ; Williams and Boon, 2019 ). NosP is also a regulator of a histidine kinase signal transduction pathway that paradoxically is also critical for optimal biofilm formation ( Williams et al, 2018 ).…”

Section: How Does Pa Sense and Combat No?mentioning

confidence: 99%

The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections

et al. 2021

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The life-threatening pandemic concerning multi-drug resistant (MDR) bacteria is an evolving problem involving increased hospitalizations, billions of dollars in medical costs and a remarkably high number of deaths. Bacterial pathogens have demonstrated the capacity for spontaneous or acquired antibiotic resistance and there is virtually no pool of organisms that have not evolved such potentially clinically catastrophic properties. Although many diseases are linked to such organisms, three include cystic fibrosis (CF), burn/blast wounds and urinary tract infections (UTIs), respectively. Thus, there is a critical need to develop novel, effective antimicrobials for the prevention and treatment of such problematic infections. One of the most formidable, naturally MDR bacterial pathogens is Pseudomonas aeruginosa (PA) that is particularly susceptible to nitric oxide (NO), a component of our innate immune response. This susceptibility sets the translational stage for the use of NO-based therapeutics during the aforementioned human infections. First, we discuss how such NO therapeutics may be able to target problematic infections in each of the aforementioned infectious scenarios. Second, we describe a recent discovery based on years of foundational information, a novel drug known as AB569. AB569 is capable of forming a “time release” of NO from S-nitrosothiols (RSNO). AB569, a bactericidal tandem consisting of acidified NaNO2 (A-NO2–) and Na2-EDTA, is capable of killing all pathogens that are associated with the aforementioned disorders. Third, we described each disease state in brief, the known or predicted effects of AB569 on the viability of PA, its potential toxicity and highly remote possibility for resistance to develop. Finally, we conclude that AB569 can be a viable alternative or addition to conventional antibiotic regimens to treat such highly problematic MDR bacterial infections for civilian and military populations, as well as the economical burden that such organisms pose.

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Bacterial Heme-Based Sensors of Nitric Oxide

Cited by 22 publications

References 113 publications

Characterization of a Cobalt-Substituted Globin-Coupled Oxygen Sensor Histidine Kinase from Anaeromyxobacter sp. Fw109-5: Insights into Catalytic Regulation by Its Heme Coordination Structure

Characterization of a Cobalt-Substituted Globin-Coupled Oxygen Sensor Histidine Kinase from Anaeromyxobacter sp. Fw109-5: Insights into Catalytic Regulation by Its Heme Coordination Structure

Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide

The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections

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