Environmental Heme-Based Sensor Proteins: Implications for Understanding Bacterial Pathogenesis

Farhana, Aisha; Saini, Vikram; Kumar, Ashwani; Lancaster, Jack R.; Steyn, Adrie J. C.

doi:10.1089/ars.2012.4613

Cited by 30 publications

(30 citation statements)

References 95 publications

(129 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…DosS and DosT (with response regulator DosR) regulate the transition of Mycobacterium tuberculosis from a replicating form to a "persistent" latent state that is unresponsive to antibiotics (87 (89). Dos regulon induction is essential for M. tuberculosis survival/recovery on exposure to hypoxia, NO, and CO, conditions faced on host infection and immune response activation (87).…”

Section: Doss and Dostmentioning

confidence: 99%

“…Dos regulon induction is essential for M. tuberculosis survival/recovery on exposure to hypoxia, NO, and CO, conditions faced on host infection and immune response activation (87). DosS/ DosT are autokinases that phosphorylate a conserved His and then transfer phosphate to DosR Asp-45 to up-regulate target genes (90).…”

Section: Doss and Dostmentioning

confidence: 99%

“…However, the in vivo situation is more complex. Differential expression of dosT (constitutive in anaerobic dormancy and in aerobic growth) and dosS (induced by hypoxia, CO, and NO) suggests that DosT induces the Dos regulon in response to hypoxia, and then DosS (induced by the action of DosT) continues to induce the regulon once DosT is inactivated (87). Ascorbate (a cytochrome c reductant) and menaquinone induce the Dos regulon under aerobic conditions, suggesting links to the M. tuberculosis respiratory chain (87).…”

Section: Doss and Dostmentioning

confidence: 99%

See 2 more Smart Citations

Heme Sensor Proteins

Girvan

Munro

2013

Journal of Biological Chemistry

128

116

View full text Add to dashboard Cite

Heme is a prosthetic group best known for roles in oxygen transport, oxidative catalysis, and respiratory electron transport. Recent years have seen the roles of heme extended to sensors of gases such as O 2 and NO and cell redox state, and as mediators of cellular responses to changes in intracellular levels of these gases. The importance of heme is further evident from identification of proteins that bind heme reversibly, using it as a signal, e.g. to regulate gene expression in circadian rhythm pathways and control heme synthesis itself. In this minireview, we explore the current knowledge of the diverse roles of heme sensor proteins. Heme-responsive Proteins: Defining FeaturesHeme homeostasis is crucial. Free heme at Ͼ1 M is cytotoxic, mainly by producing reactive oxygen species. Iron intake accounts for only a small proportion of mammalian requirements, so iron recycling (particularly from heme) is critical (1). Tight regulation of heme synthesis/breakdown is needed. Heme regulates its own fate and controls several other biological processes. Heme-responsive proteins elicit cellular responses by binding/debinding heme or via changes in heme ligation (e.g. by gases) or redox state. They can be divided into two classes: nuclear receptor (NR) 2 hemoproteins and heme sensors with no NR function. Each heme-responsive protein has a heme regulatory motif (HRM), usually containing a CP motif (2). The Cys residue of the CP motif is an axial heme ligand. No other residues are conserved across the protein class. The wider relevance of the CP motif is unclear because other hemoproteins (e.g. prostaglandin E 2 synthase, chloroperoxidase, and some cytochromes P450) also have a CP motif. The properties of members of the two main classes are described below. NR HemoproteinsSeveral heme-binding proteins occur in the NR superfamily, which is the largest transcription factor superfamily (summarized in Table 1). NRs bind specific DNA motifs in response to small molecule signaling. They generally share conserved domain architecture, with a DNA-binding region containing two zinc fingers, a ligand-binding domain, and activation domains (3). Usually, ligand binding induces conformational changes that dissociate partner proteins, allowing DNA binding and/or changes to dimerization status or cellular localization that enable the protein to elicit a response. A subfamily of NRs binds heme at their ligand-binding domain and so act as heme sensors, as discussed below. Circadian Rhythm Heme SensorsCircadian rhythms are regulated by feedback loops at transcriptional/translational levels. Heme is critical in this process (4). In vertebrates, the expression of several day/night cycle genes, as well as Rev-erb␣, is controlled by binding a heterodimer of Clock (or NPAS2 (neuronal PAS domain protein 2)) and Bmal1 to their 5Ј-UTR, thus switching on transcription. Expression of Bmal1 and NPAS2/Clock is repressed in turn by binding of Rev-erb␣ to a homodimeric partner (5). Rev-erb␣ and homologs (Rev-erb␤ and E75, with the latter involved in inse...

show abstract

Section: Doss and Dostmentioning

confidence: 99%

Section: Doss and Dostmentioning

confidence: 99%

Section: Doss and Dostmentioning

confidence: 99%

See 1 more Smart Citation

Heme Sensor Proteins

Girvan

Munro

2013

Journal of Biological Chemistry

128

116

View full text Add to dashboard Cite

show abstract

“…In general, the heme-based oxygen sensors are composed of an N-terminal heme-bound oxygen-sensing/binding domain containing globin, PAS (Per-Arnt-Sim), or GAF (cGMP-specific and cGMP-stimulated phosphodiesterases, adenylate cyclases, and Escherichia coli FhlA) folds and a C-terminal functional/catalytic domain ( Fig. 1) (7)(8)(9)(10)(11)(12)(13). O 2 (the first signal) binds to/dissociates from the heme iron complex and induces a structural change (the second signal) in the heme-bound oxygen-sensing domain of the protein.…”

Section: What Is a Heme-based Oxygen Sensor?mentioning

confidence: 99%

Heme-based Globin-coupled Oxygen Sensors: Linking Oxygen Binding to Functional Regulation of Diguanylate Cyclase, Histidine Kinase, and Methyl-accepting Chemotaxis

Martínková

Kitanishi

Shimizu

2013

Journal of Biological Chemistry

107

View full text Add to dashboard Cite

An emerging class of novel heme-based oxygen sensors containing a globin fold binds and senses environmental O 2 via a heme iron complex. Structure-function relationships of oxygen sensors containing a heme-bound globin fold are different from those containing heme-bound PAS and GAF folds. It is thus worth reconsidering from an evolutionary perspective how heme-bound proteins with a globin fold similar to that of hemoglobin and myoglobin could act as O 2 sensors. Here, we summarize the molecular mechanisms of heme-based oxygen sensors containing a globin fold in an effort to shed light on the O 2 -sensing properties and O 2 -stimulated catalytic enhancement observed for these proteins.

show abstract

“…Like heme proteins that mediate O 2 transport [90], gas sensing [91–95], and peroxidase catalysis, Clds have a proximal histidine ligand to the heme (Figure 8, left). A glutamic or aspartic acid forms a hydrogen bond to the proximal histidine’s other, unligated nitrogen.…”

Section: Oxygen Generation By Chlorite Dismutasesmentioning

confidence: 99%

Production of Dioxygen in the Dark: Dismutases of Oxyanions

DuBois

Ojha

2014

Sustaining Life on Planet Earth: Metalloenzymes Mastering Dioxygen and Other Chewy Gases

View full text Add to dashboard Cite

O2 generating reactions are exceedingly rare in biology and difficult to mimic synthetically. Perchlorate-respiring bacteria enzymatically detoxify chlorite false(normalCnormallO2−false), the end product of the perchlorate false(normalCnormallO4−false) respiratory pathway, by rapidly converting it to dioxygen (O2) and chloride (Cl−). This reaction is catalyzed by a heme-containing protein, called chlorite dismutase (Cld), which bears no structural or sequence relationships with known peroxidases or other heme proteins and is part of a large family of proteins with more than one biochemical function. The original assumptions from the 1990s that perchlorate is not a natural product and that perchlorate respiration might be confined to a taxonomically narrow group of species have been called into question, as have the roles of perchlorate respiration and Cld-mediated reactions in the global biogeochemical cycle of chlorine. In this chapter, the chemistry and biochemistry of Cld-mediated O2 generation, as well as the biological and geochemical context of this extraordinary reaction, are described.

show abstract

Environmental Heme-Based Sensor Proteins: Implications for Understanding Bacterial Pathogenesis

Cited by 30 publications

References 95 publications

Heme Sensor Proteins

Heme Sensor Proteins

Heme-based Globin-coupled Oxygen Sensors: Linking Oxygen Binding to Functional Regulation of Diguanylate Cyclase, Histidine Kinase, and Methyl-accepting Chemotaxis

Production of Dioxygen in the Dark: Dismutases of Oxyanions

Contact Info

Product

Resources

About