Sandbox Reserved 1625: Difference between revisions

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OCA, Emily Neal, Grace A. Bassler, Marisa Villarreal

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 <StructureSection  load='6rx4'  size='350'  frame='true' side='right' caption='Cartoon representation of E. coli cytochrome bd-1 oxidase designed from [https://www.rcsb.org/structure/6RX4 PDB: 6RX4]. Blue= CydA; green= CydB; yellow= CydX; pink= CydS; gray = hemes and UQ-8.' scene='83/832931/Full/3'>
 ==Introduction==
-<scene name='83/832931/Full/4'>Cytochrome bd oxidase</scene> is a type of quinol-dependent [https://en.wikipedia.org/wiki/Transmembrane_protein transmembrane] (Fig. 1) terminal [https://en.wikipedia.org/wiki/Oxidase oxidase] found exclusively in [https://en.wikipedia.org/wiki/Prokaryote prokaryotes].<ref name="Safarian">PMID: 27126043</ref>  With a very high oxygen affinity, bd oxidases play a vital role in the [https://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation] pathway in both gram-positive and gram-negative bacteria. Cytochrome ''bd'' oxidase's responsibility in the oxidative phosphorylation pathway also allows it to act as a key survival factor in the bacterial stress response against antibacterial drugs <ref name="Safarian">PMID: 31604309</ref>, hypoxia, cyanide, [https://en.wikipedia.org/wiki/Nitric_oxide nitric oxide], and H<sub>2</sub>O<sub>2</sub><ref name="Harikishore">PMID: 31939065</ref>. Given this knowledge, ''bd'' oxidases have become an area of scientific research worth pursuing as they could serve as an ideal target for antimicrobial drug development. <ref name="Boot">PMID: 28878275</ref>
+<scene name='83/832931/Full/4'>Cytochrome bd oxidases</scene> are quinol-dependent [https://en.wikipedia.org/wiki/Transmembrane_protein transmembrane] (Fig. 1) terminal [https://en.wikipedia.org/wiki/Oxidase oxidases] found exclusively in [https://en.wikipedia.org/wiki/Prokaryote prokaryotes].<ref name="Safarian">PMID: 27126043</ref>  With a very high oxygen affinity, bd oxidases play a vital role in the [https://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation] pathway in both gram-positive and gram-negative bacteria. Cytochrome ''bd'' oxidase's responsibility in the oxidative phosphorylation pathway also allows it to act as a key survival factor in the bacterial stress response against antibacterial drugs <ref name="Safarian">PMID: 31604309</ref>, hypoxia, cyanide, [https://en.wikipedia.org/wiki/Nitric_oxide nitric oxide], and H<sub>2</sub>O<sub>2</sub><ref name="Harikishore">PMID: 31939065</ref>. With their essential roles in bacterial survival, "bd" oxidases have been pursued as ideal targets for antimicrobial drug development. <ref name="Boot">PMID: 28878275</ref>
 [[Image:Pp_and_cp_of_oxdiase.png|550 px|center|thumb|''Figure 1''. Cartoon model of cytochrome bd-oxidase in ''E. coli''. Dashed lines represent borders of [https://en.wikipedia.org/wiki/Cytoplasm cytoplasmic] and [https://en.wikipedia.org/wiki/Periplasm periplasmic] regions.  A quinol bound in the periplasmic <scene name='83/832924/Q_loop/3'>Q-loop</scene> is [https://en.wikipedia.org/wiki/Redox oxidized] and releases protons into the periplasmic space, generating a [https://en.wikipedia.org/wiki/Electrochemical_gradient proton gradient].  Protons and oxygen atoms from the cytoplasmic side enter cytochrome ''bd'' oxidase through specific channels.  Oxygen is [https://en.wikipedia.org/wiki/Redox reduced] to water, which is released into the cytoplasmic space.  Blue = CydA; green = CydB; yellow = CydX; pink = CydS.  [[https://www.rcsb.org/structure/6RX4 PDB: 6RX4]]]]
 The overall mechanism of ''bd'' oxidases involves an exergonic [https://en.wikipedia.org/wiki/Dioxygen_in_biological_reactions reduction of molecular oxygen] into water (Fig. 2). During this reaction, a proton gradient is generated in order to assist in the conservation of energy. <ref name="Belevich">PMID: 17690093</ref> Unlike other terminal oxidases, bd oxidases do not use a proton pump. Instead, bd oxidases use a form of vectorial chemistry that releases protons from the quinol oxidation into the positive, periplasmic side of the membrane. Protons that are required for the water formation are then consumed from the negative, cytoplasmic side of the membrane, thus creating the previously mentioned proton gradient.
-[[Image:proton graadient.jpg|300 px|left|thumb|Figure 2: Overall schematic representation of cytochrome bd oxidase. <ref name= "Giuffre">PMID: 24486503</ref>; General display of the reduction of molecular oxygen into water using the quinol as a reducing substrate. The three hemes are located near the periplasmic space, meaning that the membrane potential is generated mainly from proton transfer from the cytoplasm towards the active site on the opposite site of the membrane. Heme b<sub>558</sub> is involved in quinol oxidation and heme d serves as the site where O2 binds and becomes reduced to H2O.]]
+[[Image:proton graadient.jpg|300 px|left|thumb|Figure 2: Overall schematic representation of the reductive cycle of cytochrome bd oxidase. <ref name= "Giuffre">PMID: 24486503</ref>; In this cycle, molecular oxygen is reduced  into water using the quinol as a reducing substrate. The three hemes essential to the electron transfer are located near the periplasmic space. Heme b<sub>558</sub> is involved in quinol oxidation and heme d serves as the site where O2 binds and becomes reduced to H2O.]]
 This page will be specifically focusing on the structure and overall function of the 6RX4 ''bd'' oxidase in [https://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']. 6RX4 is a part of the long(L) quinol-binding domain subfamily that terminal oxidases are classified into. The L-subfamily of ''bd'' oxidases are responsible for the survival of acute infectious diseases such as ''E. coli'' and [http://www.example.com salmonella]. The 6RX4's three <scene name='83/832931/Heme/4'>heme</scene> groups, its periplasmically exposed <scene name='83/832924/Q_loop/3'>Q-loop</scene>, and <scene name='83/832942/Four_subunits_labelled_6rx4/2'>four protein subunits</scene> will be of primary focus when identifying the relationship between structure and function.