User:R. Jeremy Johnson/bd Oxidase - Revision history

R. Jeremy Johnson at 20:54, 2 December 2020

R. Jeremy Johnson — Wed, 02 Dec 2020 20:54:41 GMT

←Older revision		Revision as of 20:54, 2 December 2020
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	==''bd'' oxidase ''Escherichia coli''==		==''bd'' oxidase ''Escherichia coli''==
-	''bd'' oxidase from [https://en.wikipedia.org/wiki/Escherichia_coli ''E. coli''] is part of the long(L) quinol-binding domain subfamily of terminal oxidases (<scene name='83/832931/Full/3'>Overview</scene> "bd" oxidase ''Escherichia coli''). The L-subfamily of ''bd'' oxidases are responsible for the survival of acute infectious pathogens such as ''E. coli'' and [https://en.wikipedia.org/wiki/Salmonella ''Salmonella'']. The cytochrome ''bd'' oxidase'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_6rx4/3'>four protein subunits</scene> will be the primary focus when explaining how the structure of ''bd'' oxidase allows it to catalyze the reduction of molecular oxygen into water and how the structure of the ''E. coli'' ''bd'' oxidase differs from ''G. thermodenitrificans'' ''bd'' oxidase.	+	''bd'' oxidase from [https://en.wikipedia.org/wiki/Escherichia_coli ''E. coli''] is part of the long(L) quinol-binding domain subfamily of terminal oxidases (<scene name='83/832931/Full/3'>Overview</scene> ''bd'' oxidase ''Escherichia coli''). The L-subfamily of ''bd'' oxidases are responsible for the survival of acute infectious pathogens such as ''E. coli'' and [https://en.wikipedia.org/wiki/Salmonella ''Salmonella'']. The cytochrome ''bd'' oxidase'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_6rx4/3'>four protein subunits</scene> will be the primary focus when explaining how the structure of ''bd'' oxidase allows it to catalyze the reduction of molecular oxygen into water and how the structure of the ''E. coli'' ''bd'' oxidase differs from ''G. thermodenitrificans'' ''bd'' oxidase.

	==Structure==		==Structure==

R. Jeremy Johnson at 20:44, 2 December 2020

R. Jeremy Johnson — Wed, 02 Dec 2020 20:44:25 GMT

←Older revision		Revision as of 20:44, 2 December 2020
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	== 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 more poorly when compared 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-α][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>	+	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 more poorly when compared 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-α]][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.

R. Jeremy Johnson at 20:43, 2 December 2020

R. Jeremy Johnson — Wed, 02 Dec 2020 20:43:21 GMT

(Difference between revisions)

R. Jeremy Johnson at 18:32, 5 May 2020

R. Jeremy Johnson — Tue, 05 May 2020 18:32:25 GMT

R. Jeremy Johnson at 18:22, 5 May 2020

R. Jeremy Johnson — Tue, 05 May 2020 18:22:10 GMT

(Difference between revisions)

R. Jeremy Johnson at 18:15, 5 May 2020

R. Jeremy Johnson — Tue, 05 May 2020 18:15:58 GMT

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R. Jeremy Johnson at 17:57, 5 May 2020

R. Jeremy Johnson — Tue, 05 May 2020 17:57:04 GMT

←Older revision		Revision as of 17:57, 5 May 2020
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-	__NoTOC__== Cytochrome ''bd'' oxidase ==	+	__NoTOC__= Cytochrome ''bd'' oxidase =
	<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'>		<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==		==Introduction==

R. Jeremy Johnson at 17:56, 5 May 2020

R. Jeremy Johnson — Tue, 05 May 2020 17:56:43 GMT

←Older revision		Revision as of 17:56, 5 May 2020
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	__NoTOC__== Cytochrome ''bd'' oxidase ==		__NoTOC__== Cytochrome ''bd'' oxidase ==
-	<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'> ~~__NoTOC__~~	+	<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==		==Introduction==
	<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>		<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>

R. Jeremy Johnson at 17:55, 5 May 2020

R. Jeremy Johnson — Tue, 05 May 2020 17:55:56 GMT

←Older revision		Revision as of 17:55, 5 May 2020
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-	== Cytochrome ''bd'' oxidase ==	+	__NoTOC__== Cytochrome ''bd'' oxidase ==
	<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'> __NoTOC__		<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'> __NoTOC__
	==Introduction==		==Introduction==

R. Jeremy Johnson at 17:55, 5 May 2020

R. Jeremy Johnson — Tue, 05 May 2020 17:55:34 GMT

←Older revision		Revision as of 17:55, 5 May 2020
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	== Cytochrome ''bd'' oxidase ==		== Cytochrome ''bd'' oxidase ==
-	<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'> ~~</TOC>~~	+	<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'> __NoTOC__
	==Introduction==		==Introduction==
	<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>		<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>

←Older revision		Revision as of 18:32, 5 May 2020
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	[https://www.uniprot.org/proteomes/UP000001578 ''G. thermodenitrificans''] is a facultative aerobic thermophilic bacterium that utilizes the bd oxidase mechanism (<scene name='83/838655/Bdoxidase_structure_full/3'>Overview</scene> "bd" oxidase ''Geobacillus thermodenitrificans''). The oxygen enters the enzyme through the selective <scene name='83/832926/Potential_oxygen_entry_site/2'>oxygen entry site</scene> that funnels the extracellular oxygen to <scene name='83/838655/Bd_oxidase_heme_d/2'>Heme D</scene> in the active site. The electrons for the reaction are provided by a ubiquinone molecule bound to the <scene name='83/838655/Bdoxidase_q_loop/3'>Q loop</scene>. The protons for the reaction are provided by one of two <scene name='83/838655/Bdoxidase_proton_pathways/1'>potential proton pathways</scene>, either the <scene name='83/838655/Bdoxidase_cyda_pathway/6'>CydA pathway</scene> or <scene name='83/838655/Bdoxidase_cydb_pathway/3'>CydB pathway</scene>. Both of the proton pathways utilize the intracellular water molecules for the proton source, and shuttle them to <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene>.		[https://www.uniprot.org/proteomes/UP000001578 ''G. thermodenitrificans''] is a facultative aerobic thermophilic bacterium that utilizes the bd oxidase mechanism (<scene name='83/838655/Bdoxidase_structure_full/3'>Overview</scene> "bd" oxidase ''Geobacillus thermodenitrificans''). The oxygen enters the enzyme through the selective <scene name='83/832926/Potential_oxygen_entry_site/2'>oxygen entry site</scene> that funnels the extracellular oxygen to <scene name='83/838655/Bd_oxidase_heme_d/2'>Heme D</scene> in the active site. The electrons for the reaction are provided by a ubiquinone molecule bound to the <scene name='83/838655/Bdoxidase_q_loop/3'>Q loop</scene>. The protons for the reaction are provided by one of two <scene name='83/838655/Bdoxidase_proton_pathways/1'>potential proton pathways</scene>, either the <scene name='83/838655/Bdoxidase_cyda_pathway/6'>CydA pathway</scene> or <scene name='83/838655/Bdoxidase_cydb_pathway/3'>CydB pathway</scene>. Both of the proton pathways utilize the intracellular water molecules for the proton source, and shuttle them to <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene>.

-	The <scene name='83/838655/Bdoxidase_structure_full/4'>''G. thermodenitrificans'' overall structure</scene> contains <scene name='83/838655/Bdoxidase_only_helicies/2'> 19 transmembrane helices</scene> that are arranged in a nearly oval shape.<ref name = ~~”Safarian 2016”~~ /> The protein contains two structurally similar subunits, <scene name='83/838655/Bdoxidase_cyda_subunit/2'>CydA</scene>, seen in <font color='blue'><b>blue</b></font>, and <scene name='83/838655/Bdoxidase_cydb_subunit/2'>CydB</scene>, seen in <font color='red'><b>red</b></font>, each containing nine helices, and one smaller subunit, <scene name='83/838655/Bdoxidase_cydx_subunit/2'>CydX</scene>, in <font color='teal'><b>teal</b></font>, with one transmembrane helix. These subunits interact using hydrophobic residues and symmetry at the interfaces. The CydX subunit, whose function is not currently known, is positioned in the same way as CydS, a separate subunit that is found in the bd oxidase homologue from [https://www.rcsb.org/structure/6RKO ''E. coli'' bd oxidase], but is not found in ''G. thermodenitrificans''. Due to its similar structure and position to CydS, CydX has been hypothesized to potentially stabilize <scene name='83/838655/Bd_oxidase_heme_558/3'>Heme B558</scene> during potential structural rearrangements of the Q loop upon binding and oxidation of ubiquinone (Figure 1), the function of CydS in [https://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']<ref name = ~~”Safarian 2019”~~ /> The <scene name='83/838655/Bdoxidase_q_loop/3'>Q loop</scene> is a hydrophilic region above Cyd A. The lack of [https://en.wikipedia.org/wiki/Hydrogen_bond hydrogen bonding] in this hydrophobic protein allows the protein to be flexible and go through a large conformational change for reduction of dioxygen. <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene> is mostly involved in the proton pathway, and <scene name='83/838655/Bd_oxidase_heme_d/2'>Heme D</scene> is involved with the oxygen pathway.	+	The <scene name='83/838655/Bdoxidase_structure_full/4'>''G. thermodenitrificans'' overall structure</scene> contains <scene name='83/838655/Bdoxidase_only_helicies/2'> 19 transmembrane helices</scene> that are arranged in a nearly oval shape.<ref name = "Safarian 2016" /> The protein contains two structurally similar subunits, <scene name='83/838655/Bdoxidase_cyda_subunit/2'>CydA</scene>, seen in <font color='blue'><b>blue</b></font>, and <scene name='83/838655/Bdoxidase_cydb_subunit/2'>CydB</scene>, seen in <font color='red'><b>red</b></font>, each containing nine helices, and one smaller subunit, <scene name='83/838655/Bdoxidase_cydx_subunit/2'>CydX</scene>, in <font color='teal'><b>teal</b></font>, with one transmembrane helix. These subunits interact using hydrophobic residues and symmetry at the interfaces. The CydX subunit, whose function is not currently known, is positioned in the same way as CydS, a separate subunit that is found in the bd oxidase homologue from [https://www.rcsb.org/structure/6RKO ''E. coli'' bd oxidase], but is not found in ''G. thermodenitrificans''. Due to its similar structure and position to CydS, CydX has been hypothesized to potentially stabilize <scene name='83/838655/Bd_oxidase_heme_558/3'>Heme B558</scene> during potential structural rearrangements of the Q loop upon binding and oxidation of ubiquinone (Figure 1), the function of CydS in [https://en.wikipedia.org/wiki/Escherichia_coli ''E. coli'']<ref name = "Safarian 2019" /> The <scene name='83/838655/Bdoxidase_q_loop/3'>Q loop</scene> is a hydrophilic region above Cyd A. The lack of [https://en.wikipedia.org/wiki/Hydrogen_bond hydrogen bonding] in this hydrophobic protein allows the protein to be flexible and go through a large conformational change for reduction of dioxygen. <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene> is mostly involved in the proton pathway, and <scene name='83/838655/Bd_oxidase_heme_d/2'>Heme D</scene> is involved with the oxygen pathway.

	==Structure==		==Structure==
	===Active Site===		===Active Site===
	[[Image:Hemes2.png\|300 px\|right\|thumb\|Figure 1. The active site of bd oxidase for ''G. thermodenitrificans''. Heme B558 (pink; left), Heme B595 (pink; right), and Heme D (green). Important residues shown in blue. Measurements are shown in Å.]]		[[Image:Hemes2.png\|300 px\|right\|thumb\|Figure 1. The active site of bd oxidase for ''G. thermodenitrificans''. Heme B558 (pink; left), Heme B595 (pink; right), and Heme D (green). Important residues shown in blue. Measurements are shown in Å.]]
-	The active site for bd oxidase in ''G. thermodenitrificans'' is located in subunit Cyd A. The site consists of three iron hemes: <scene name='83/838655/Bd_oxidase_heme_558/3'>Heme B558</scene>, <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene>, and <scene name='83/838655/Bd_oxidase_heme_d/2'>Heme D</scene> that are held together in a rigid triangular <scene name='83/838655/Hemes/8'>arrangement</scene> due to [https://en.wikipedia.org/wiki/Van_der_Waals_force Van der Waals interactions].<ref name = ~~”Safarian 2016”~~ /> The <scene name='83/838655/Hemes_measurements/5'>length</scene> between each heme's central iron is relatively constant which serves to shuttle protons and electrons from one heme to another efficiently (Figure 1). <scene name='83/838655/Bd_oxidase_heme_558/3'>Heme B558</scene> is hypothesized to act as an electron acceptor, orientated toward the extracellular side by <scene name='83/838655/Bdoxidase_structure_heme/4'>His 186, Met 325, and Lys 252</scene> (Figure 1).<ref name = ~~”Safarian 2016”~~ /> With <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene> closest in proximity to the intracellular side, Heme B559 is likely the proton acceptor with two potential proton pathways. Both <scene name='83/838655/Bd_oxidase_heme_558/3'>Heme B558</scene> and <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene> then shuttle their respective ions directly to <scene name='83/838655/Bd_oxidase_heme_d/2'>Heme D</scene> as this is the shortest pathway.	+	The active site for bd oxidase in ''G. thermodenitrificans'' is located in subunit Cyd A. The site consists of three iron hemes: <scene name='83/838655/Bd_oxidase_heme_558/3'>Heme B558</scene>, <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene>, and <scene name='83/838655/Bd_oxidase_heme_d/2'>Heme D</scene> that are held together in a rigid triangular <scene name='83/838655/Hemes/8'>arrangement</scene> due to [https://en.wikipedia.org/wiki/Van_der_Waals_force Van der Waals interactions].<ref name = "Safarian 2016" /> The <scene name='83/838655/Hemes_measurements/5'>length</scene> between each heme's central iron is relatively constant which serves to shuttle protons and electrons from one heme to another efficiently (Figure 1). <scene name='83/838655/Bd_oxidase_heme_558/3'>Heme B558</scene> is hypothesized to act as an electron acceptor, orientated toward the extracellular side by <scene name='83/838655/Bdoxidase_structure_heme/4'>His 186, Met 325, and Lys 252</scene> (Figure 1).<ref name = "Safarian 2016" /> With <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene> closest in proximity to the intracellular side, Heme B559 is likely the proton acceptor with two potential proton pathways. Both <scene name='83/838655/Bd_oxidase_heme_558/3'>Heme B558</scene> and <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene> then shuttle their respective ions directly to <scene name='83/838655/Bd_oxidase_heme_d/2'>Heme D</scene> as this is the shortest pathway.

	===Potential Oxygen Entry Site===		===Potential Oxygen Entry Site===
Line 21:		Line 21:

	===Electron Source===		===Electron Source===
-	An electron source is needed in order for the redox reaction of O₂ to occur. Cytochrome bd oxidase uses the quinol molecule [https://en.wikipedia.org/wiki/Coenzyme_Q10 ubiquinone] as an electron donor (Figure 2). [[Image:Ubiquinone.jpg\|200 px\|right\|thumb\|Figure 2. Chemical structure of ubiquinone.]] As shown in the <scene name='83/838655/Bdoxidase_structure_full/4'>overall structure</scene>, the <scene name='83/838655/Bdoxidase_q_loop/3'>Q loop</scene> is on the extracellular surface and provides a binding site for ubiquinone.<ref name = ~~”Safarian 2016”~~ /> Heme <scene name='83/838655/Bdoxidase_qloop_zoom/3'>B558 is closest in proximity to the Q loop</scene> and thus is the suggested [https://en.wikipedia.org/wiki/Electron_acceptor electron acceptor]. This suggestion is further supported by the <scene name='83/838655/Bdoxidase_trp/2'>conservation of Trp374</scene> often found as intermediate electron receptors in biological [https://en.wikipedia.org/wiki/Electron_transport_chain electron transfer chains].<ref name =~~”Safarian 2016”~~ />	+	An electron source is needed in order for the redox reaction of O₂ to occur. Cytochrome bd oxidase uses the quinol molecule [https://en.wikipedia.org/wiki/Coenzyme_Q10 ubiquinone] as an electron donor (Figure 2). [[Image:Ubiquinone.jpg\|200 px\|right\|thumb\|Figure 2. Chemical structure of ubiquinone.]] As shown in the <scene name='83/838655/Bdoxidase_structure_full/4'>overall structure</scene>, the <scene name='83/838655/Bdoxidase_q_loop/3'>Q loop</scene> is on the extracellular surface and provides a binding site for ubiquinone.<ref name = "Safarian 2016" /> Heme <scene name='83/838655/Bdoxidase_qloop_zoom/3'>B558 is closest in proximity to the Q loop</scene> and thus is the suggested [https://en.wikipedia.org/wiki/Electron_acceptor electron acceptor]. This suggestion is further supported by the <scene name='83/838655/Bdoxidase_trp/2'>conservation of Trp374</scene> often found as intermediate electron receptors in biological [https://en.wikipedia.org/wiki/Electron_transport_chain electron transfer chains].<ref name ="Safarian 2016" />

	===Potential Proton Pathways===		===Potential Proton Pathways===
Line 27:		Line 27:
	Because there is no proton pump present, the proton transfer mechanism is facilitated by <scene name='83/838655/Bdoxidase_proton_pathways/1'>2 potential proton pathways</scene> via intracellular water molecules.		Because there is no proton pump present, the proton transfer mechanism is facilitated by <scene name='83/838655/Bdoxidase_proton_pathways/1'>2 potential proton pathways</scene> via intracellular water molecules.

-	One potential proton pathway is formed from the <scene name='83/838655/Bdoxidase_helix_a_1-4/1'>four-helix bundle (a1-4)</scene> of <scene name='83/838655/Bdoxidase_cyda_subunit/2'>CydA</scene>. It is called the <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/1'>CydA pathway</scene>. The residues along this pathway help facilitate the movement of the protons. The location and negative charge characteristic of <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/2'>Glu108</scene>, together with previous mutagenesis experiments, supports the proposal that this glutamate residue is a redox state-dependent mediator of proton transfer to a charge compensation site. In other words, it acts like a proton shuttle.<ref name =~~”Safarian 2016”~~ /> The <scene name='83/838655/Bdoxidase_cyda_pathway_glu101/1'>Glu101 residue</scene>, which is the last residue in this pathway, could be the protonatable group eventually used upon <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene> reduction. More research needs to be done to determine whether the CydA pathway is solely providing protons for charge compensation, or whether <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/2'>Glu108</scene> can be a branching point that is able to pass protons via the <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene> propionates to the oxygen-binding site.<ref name=~~”Safarian 2016”~~ />	+	One potential proton pathway is formed from the <scene name='83/838655/Bdoxidase_helix_a_1-4/1'>four-helix bundle (a1-4)</scene> of <scene name='83/838655/Bdoxidase_cyda_subunit/2'>CydA</scene>. It is called the <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/1'>CydA pathway</scene>. The residues along this pathway help facilitate the movement of the protons. The location and negative charge characteristic of <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/2'>Glu108</scene>, together with previous mutagenesis experiments, supports the proposal that this glutamate residue is a redox state-dependent mediator of proton transfer to a charge compensation site. In other words, it acts like a proton shuttle.<ref name ="Safarian 2016" /> The <scene name='83/838655/Bdoxidase_cyda_pathway_glu101/1'>Glu101 residue</scene>, which is the last residue in this pathway, could be the protonatable group eventually used upon <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene> reduction. More research needs to be done to determine whether the CydA pathway is solely providing protons for charge compensation, or whether <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/2'>Glu108</scene> can be a branching point that is able to pass protons via the <scene name='83/838655/Bd_oxidase_heme_b_595/2'>Heme B595</scene> propionates to the oxygen-binding site.<ref name="Safarian 2016" />

-	Another potential entry site is close to the <scene name='83/838655/Bdoxidase_cydb_subunit_b1-4/1'>a1-4 four-helix bundle</scene> of <scene name='83/838655/Bdoxidase_cydb_subunit/2'>CydB</scene> and is referred to as the <scene name='83/838655/Bdoxidase_cydb_pathway/3'>CydB pathway</scene>. In this pathway, <scene name='83/838655/Bdoxidase_cydb_pathway_asp25/1'>Asp25</scene> is thought to be the equivalent of the <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/2'>Glu108</scene> in the CydA pathway.<ref name =~~”Safarian 2016”~~ /> The other residues help facilitate the movement of the proton very similarly to the <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/1'>CydA pathway</scene>. The <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/1'>CydA pathway</scene> is the most accepted source of protons as less is known about the <scene name='83/838655/Bdoxidase_cydb_pathway/3'>CydB pathway</scene>.	+	Another potential entry site is close to the <scene name='83/838655/Bdoxidase_cydb_subunit_b1-4/1'>a1-4 four-helix bundle</scene> of <scene name='83/838655/Bdoxidase_cydb_subunit/2'>CydB</scene> and is referred to as the <scene name='83/838655/Bdoxidase_cydb_pathway/3'>CydB pathway</scene>. In this pathway, <scene name='83/838655/Bdoxidase_cydb_pathway_asp25/1'>Asp25</scene> is thought to be the equivalent of the <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/2'>Glu108</scene> in the CydA pathway.<ref name ="Safarian 2016" /> The other residues help facilitate the movement of the proton very similarly to the <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/1'>CydA pathway</scene>. The <scene name='83/838655/Bdoxidase_cyda_pathway_glu108/1'>CydA pathway</scene> is the most accepted source of protons as less is known about the <scene name='83/838655/Bdoxidase_cydb_pathway/3'>CydB pathway</scene>.

	== Overall Oxygen Reduction Mechanism in ''G. thermodenitrificans''==		== Overall Oxygen Reduction Mechanism in ''G. thermodenitrificans''==