Sandbox Reserved 1625: Difference between revisions
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Quinol is used as the initial [https://en.wikipedia.org/wiki/Electron_donor electron donor] and heme b<sub>558</sub> is the initial electron acceptor. <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/1'>H-channel</scene> collects protons and <scene name='83/832931/O_channel_overall/2'>O-channel</scene> collects oxygen atoms that flow to 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''. Summarized 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 is used as the initial [https://en.wikipedia.org/wiki/Electron_donor electron donor] and heme b<sub>558</sub> is the initial electron acceptor. <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/1'>H-channel</scene> collects protons and <scene name='83/832931/O_channel_overall/2'>O-channel</scene> collects oxygen atoms that flow to 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''. Summarized 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 | The cytochrome ''bd'' oxidase is essential for [https://en.wikipedia.org/wiki/Pathogenic_bacteria pathogenic bacteria] to thrive in the human body by enhancing bacterial growth and [https://en.wikipedia.org/wiki/Colonisation_(biology) 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'' were missing or possessed ineffective CydA and B subunits, bacterial growth ceased.<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 wild type levels of colonization<ref name="Hughes">PMID: 28182951</ref>. The cytochrome ''bd'' oxidase is the main component in nitric oxide (NO) tolerance in bacteria, which is released by neutrophils and macrophages when the host is infected<ref name="Shepherd">PMID: 27767067</ref>. ''E. coli'' growth seen in 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 imidazo[1,2-α]pyridine, a known inhibitor of respiratory enzymes<ref name="Arora">PMID:25155596</ref>. Upregulation of the cytochrome ''bd'' oxidase Cyd genes resulted in a mutant strain of ''M. tb'' that was 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 pathogenic bacterial infections, inhibitors that target cytochrome ''bd'' oxidase are promising antibacterial agents. Compounds that target heme b<sub>558</sub><ref name="Harikishore">PMID: 31939065</ref>, create 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 pathogenic bacterial infections, inhibitors that target cytochrome ''bd'' oxidase are promising antibacterial agents. Compounds that target heme b<sub>558</sub><ref name="Harikishore">PMID: 31939065</ref>, create 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. | ||