Sandbox Reserved 1605: Difference between revisions
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Quinol transfers two electrons to heme b<sub>558</sub> and releases two protons into the periplasmic space as the initial [https://en.wikipedia.org/wiki/Electron_donor electron donor]. <scene name='83/832931/Heme/6'>Heme b558</scene> transfers the electrons to <scene name='83/832931/Heme/6'>heme b595</scene>, which transfers the electrons to <scene name='83/832931/Heme/6'>heme d</scene>. Concurrently, the <scene name='83/832931/Overall_h_channel/2'>H-channel</scene> collects protons from the cytoplasmic side using the proton gradient and the <scene name='83/832931/O_channel_overall/3'>O-channel</scene> collects oxygen atoms. The protons and oxygen flow to the active site heme d (Fig. 3). With electrons, oxygen, and protons available, heme d can successfully reduce dioxygen to water (Fig. 2, 4). [[Image:mech4.png|500 px|center|thumb|''Figure 4''. General mechanism of cytochrome bd-oxidase in ''E. coli''. Electrons are passed from quinol to heme b<sub>558</sub> to heme b<sub>595</sub> to heme d. Protons and oxygen atoms flow into the H-channel and O-channel to heme d. Heme d catalzyes the reduction of oxygen to water.]] | Quinol transfers two electrons to heme b<sub>558</sub> and releases two protons into the periplasmic space as the initial [https://en.wikipedia.org/wiki/Electron_donor electron donor]. <scene name='83/832931/Heme/6'>Heme b558</scene> transfers the electrons to <scene name='83/832931/Heme/6'>heme b595</scene>, which transfers the electrons to <scene name='83/832931/Heme/6'>heme d</scene>. Concurrently, the <scene name='83/832931/Overall_h_channel/2'>H-channel</scene> collects protons from the cytoplasmic side using the proton gradient and the <scene name='83/832931/O_channel_overall/3'>O-channel</scene> collects oxygen atoms. The protons and oxygen flow to the active site heme d (Fig. 3). With electrons, oxygen, and protons available, heme d can successfully reduce dioxygen to water (Fig. 2, 4). [[Image:mech4.png|500 px|center|thumb|''Figure 4''. General mechanism of cytochrome bd-oxidase in ''E. coli''. Electrons are passed from quinol to heme b<sub>558</sub> to heme b<sub>595</sub> to heme d. Protons and oxygen atoms flow into the H-channel and O-channel to heme d. Heme d catalzyes the reduction of oxygen to water.]] | ||
== Relevance == | == Relevance == | ||
The cytochrome ''bd'' oxidase is essential for [https://en.wikipedia.org/wiki/Pathogenic_bacteria pathogenic bacteria] to thrive in the human body because it enhances bacterial growth and [https://en.wikipedia.org/wiki/Bacterial_growth colonization]. Any alteration of the ''bd'' oxidase Cyd subunits will most likely produce a nonfunctional [https://en.wikipedia.org/wiki/Mutant mutant] cytochrome ''bd'' oxidase<ref name="Moosa">PMID: 28760899</ref>, which inhibits bacterial growth. If ''E. coli'' are missing or possess ineffective CydA and B subunits, bacterial growth ceases.<ref name="Hughes">PMID: 28182951</ref>. With [https://en.wikipedia.org/wiki/Colitis colitis], ''E. coli'' mutants that were missing CydAB colonized poorly in comparison to the [https://en.wikipedia.org/wiki/Wild_type wild type] levels of colonization<ref name="Hughes">PMID: 28182951</ref>. The cytochrome ''bd'' oxidase is the main component in [https://en.wikipedia.org/wiki/Biological_functions_of_nitric_oxide#Effects_in_bacteria nitric oxide] (NO) tolerance in bacteria, which is released by [https://en.wikipedia.org/wiki/Neutrophil neutrophils] and [https://en.wikipedia.org/wiki/Macrophage macrophages] when the [https://en.wikipedia.org/wiki/Host_(biology) host] is infected<ref name="Shepherd">PMID: 27767067</ref>. ''E. coli'' growth seen in [https://en.wikipedia.org/wiki/Urinary_tract_infection urinary tract infections] is mainly due to the NO resistant ''bd'' oxidase. Without the CydA and CydB subunits, bacteria could not colonize in high NO conditions<ref name="Shepherd">PMID: 27767067</ref>. Cytochrome ''bd'' oxidases are essential for life in other pathogenic bacteria such as [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']. Deletion of the CydA and CydB subunits dramatically decreased the growth of ''M. tb'' compared to the wild type when exposed to [https://en.wikipedia.org/wiki/Imidazopyridine | The cytochrome ''bd'' oxidase is essential for [https://en.wikipedia.org/wiki/Pathogenic_bacteria pathogenic bacteria] to thrive in the human body because it enhances bacterial growth and [https://en.wikipedia.org/wiki/Bacterial_growth colonization]. Any alteration of the ''bd'' oxidase Cyd subunits will most likely produce a nonfunctional [https://en.wikipedia.org/wiki/Mutant mutant] cytochrome ''bd'' oxidase<ref name="Moosa">PMID: 28760899</ref>, which inhibits bacterial growth. If ''E. coli'' are missing or possess ineffective CydA and B subunits, bacterial growth ceases.<ref name="Hughes">PMID: 28182951</ref>. With [https://en.wikipedia.org/wiki/Colitis colitis], ''E. coli'' mutants that were missing CydAB colonized poorly in comparison to the [https://en.wikipedia.org/wiki/Wild_type wild type] levels of colonization<ref name="Hughes">PMID: 28182951</ref>. The cytochrome ''bd'' oxidase is the main component in [https://en.wikipedia.org/wiki/Biological_functions_of_nitric_oxide#Effects_in_bacteria nitric oxide] (NO) tolerance in bacteria, which is released by [https://en.wikipedia.org/wiki/Neutrophil neutrophils] and [https://en.wikipedia.org/wiki/Macrophage macrophages] when the [https://en.wikipedia.org/wiki/Host_(biology) host] is infected<ref name="Shepherd">PMID: 27767067</ref>. ''E. coli'' growth seen in [https://en.wikipedia.org/wiki/Urinary_tract_infection urinary tract infections] is mainly due to the NO resistant ''bd'' oxidase. Without the CydA and CydB subunits, bacteria could not colonize in high NO conditions<ref name="Shepherd">PMID: 27767067</ref>. Cytochrome ''bd'' oxidases are essential for life in other pathogenic bacteria such as [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''M. tuberculosis'']. Deletion of the CydA and CydB subunits dramatically decreased the growth of ''M. tb'' compared to the wild type when exposed to [https://en.wikipedia.org/wiki/Imidazopyridine imidazo[1,2-]][https://en.wikipedia.org/wiki/Imidazopyridine pyridine], a known [https://en.wikipedia.org/wiki/Enzyme_inhibitor inhibitor] of respiratory enzymes<ref name="Arora">PMID:25155596</ref>. [https://en.wikipedia.org/wiki/Downregulation_and_upregulation Upregulation] of the cytochrome ''bd'' oxidase Cyd genes resulted in a mutant strain of ''M. tb'' that was [https://en.wikipedia.org/wiki/Antimicrobial_resistance resistant] to imidazo[1,2-α]pyridine<ref name="Arora">PMID:25155596</ref>. | ||
Since cytochrome ''bd'' oxidases are only found in prokaryotes and are required for [https://en.wikipedia.org/wiki/Infection#Bacterial_or_viral pathogenic bacterial infections], inhibitors that target cytochrome ''bd'' oxidase are promising [https://en.wikipedia.org/wiki/Antibiotic antibacterial] agents. Compounds that target heme b<sub>558</sub><ref name="Harikishore">PMID: 31939065</ref>, create [https://en.wikipedia.org/wiki/Allotropes_of_oxygen unusable forms of oxygen]<ref name="Galván">PMID: 30790617</ref>, and target the o-channel <ref name="Lu">PMID: 26015371 </ref> have shown potential in halting bacterial growth. | Since cytochrome ''bd'' oxidases are only found in prokaryotes and are required for [https://en.wikipedia.org/wiki/Infection#Bacterial_or_viral pathogenic bacterial infections], inhibitors that target cytochrome ''bd'' oxidase are promising [https://en.wikipedia.org/wiki/Antibiotic antibacterial] agents. Compounds that target heme b<sub>558</sub><ref name="Harikishore">PMID: 31939065</ref>, create [https://en.wikipedia.org/wiki/Allotropes_of_oxygen unusable forms of oxygen]<ref name="Galván">PMID: 30790617</ref>, and target the o-channel <ref name="Lu">PMID: 26015371 </ref> have shown potential in halting bacterial growth. | ||