Sandbox Reserved 1625: Difference between revisions

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=== H and O channels ===

[[Image:O_AND_H_CHANNEL.png|300 px|right|thumb|'''Figure 3'''. H and o-channels of cytochrome bd-oxidase in ''E. coli''. Channels are outlined in gray, water is shown as spheres, and various amino acids are labeled above. [[https://www.rcsb.org/structure/6RX4 PDB:6RX4]]]]

The hydrogen and oxygen channels (Fig. 3) are essential for H+ and O2 molecules to reach the active site of cytochrome ''bd'' oxidase. A [https://en.wikipedia.org/wiki/Chemiosmosis#The_proton-motive_force proton motive force] generated by the oxidase<ref name= "Safarian">PMID:31604309</ref> allows protons from the cytoplasm to flow through a hydrophilic <scene name='83/832931/Overall_h_channel/2'>H-channel</scene> full of water (pink dots), entering at <scene name='83/832931/Start_of_h_channel/2'>Asp119A</scene> and moving past <scene name='83/832931/Start_of_h_channel/2'>Lys57A, Lys109B, Asp105B, Tyr379B, and Asp58B</scene><ref name="Alexander">PMID:31723136</ref> where they can be transferred to the active site with the help of the conserved residues <scene name='83/832931/End_of_h_channel/4'>Ser108A, Glu107A, and Ser140A</scene><ref name= "Safarian">PMID:31604309</ref>. A smaller <scene name='83/832931/O_channel_overall/3'>O-channel</scene> also exists that transitions from hydrophobic to hydrophilic as it gets closer to the active site. This channel allows oxygen to reach the active site, starting near <scene name='83/832931/Ochannel/2'>Trp63</scene> in CydB and passing by <scene name='83/832931/Ochannel/2'>Ile144A, Leu101A, and Glu99A</scene><ref name= "Safarian">PMID:31604309</ref>, which assists with the binding of oxygen to the active site. The o-channel channel is approximately 1.5 [https://en.wikipedia.org/wiki/Angstrom Å] in diameter<ref name="Alexander">PMID:31723136</ref>, which may help with [https://en.wikipedia.org/wiki/Chemical_specificity selectivity].

The hydrogen and oxygen channels (Fig. 3) are essential for H+ and O2 molecules to reach the active site of cytochrome ''bd'' oxidase. A [https://en.wikipedia.org/wiki/Chemiosmosis#The_proton-motive_force proton motive force] generated by the oxidase<ref name= "Safarian">PMID:31604309</ref> allows protons from the cytoplasm to flow through a hydrophilic <scene name='83/832931/Overall_h_channel/2'>H-channel</scene> full of water (pink dots), entering at <scene name='83/832931/Start_of_h_channel/2'>Asp119A</scene> and moving past <scene name='83/832931/Start_of_h_channel/2'>Lys57A, Lys109B, Asp105B, Tyr379B, and Asp58B</scene><ref name="Alexander">PMID:31723136</ref> where they can be transferred to the active site with the help of the conserved residues <scene name='83/832931/End_of_h_channel/4'>Ser108A, Glu107A, and Ser140A</scene><ref name= "Safarian">PMID:31604309</ref>. A smaller <scene name='83/832931/O_channel_overall/3'>O-channel</scene> also exists that transitions from hydrophobic to hydrophilic as it gets closer to the active site. This channel allows oxygen to reach the active site, starting near <scene name='83/832931/Ochannel/2'>Trp63</scene> in CydB and passing by <scene name='83/832931/Ochannel/2'>Ile144A, Leu101A, and Glu99A</scene><ref name= "Safarian">PMID:31604309</ref>, which assists with the binding of oxygen to the active site. The O-channel channel is approximately 1.5 [https://en.wikipedia.org/wiki/Angstrom Å] in diameter<ref name="Alexander">PMID:31723136</ref>, which may help with [https://en.wikipedia.org/wiki/Chemical_specificity selectivity].

Interestingly, the O-channel does not exist in the cytochrome ''bd'' oxidase of [https://www.rcsb.org/structure/5DOQ ''Geobacillus thermodenitrificans'']; instead, oxygen binds directly to the active site<ref name="Safarian2">PMID: 27126043</ref>. The <scene name='83/832931/Cyds/1'>CydS</scene> subunit found in E. coli blocks this alternate oxygen entry site, which allows oxygen to travel through the O-channel<ref name="Safarian">PMID:31604309</ref><ref name="Alexander">PMID:31723136</ref>. The presence of an o-channel affects oxidase activity, as the ''E. coli'' oxidase acts as a "true" oxidase, while the ''G. thermodenitrificans'' bd oxidase contributes more to detoxification<ref name="Alexander">PMID:31723136</ref>.

Interestingly, the O-channel does not exist in the cytochrome ''bd'' oxidase of [https://www.rcsb.org/structure/5DOQ ''Geobacillus thermodenitrificans'']; instead, oxygen binds directly to the active site<ref name="Safarian2">PMID: 27126043</ref>. The <scene name='83/832931/Cyds/1'>CydS</scene> subunit found in ''E. coli'' blocks this alternate oxygen entry site, which allows oxygen to travel through the O-channel<ref name="Safarian">PMID:31604309</ref><ref name="Alexander">PMID:31723136</ref>. The presence of an O-channel affects oxidase activity, as the ''E. coli'' oxidase acts as a "true" oxidase, while the ''G. thermodenitrificans'' bd oxidase contributes more to detoxification<ref name="Alexander">PMID:31723136</ref>.

=== Hemes ===

Three <scene name='83/832931/Heme/6'>hemes</scene> are present in the CydA subunit. These three hemes form a triangle to maximize subunit stability<ref name="Safarian">PMID:31604309</ref><ref name="Alexander">PMID:31723136</ref><ref name="Safarian2">PMID:27126043</ref>, which is an evolutionary conserved feature across bd oxidases<ref name="Safarian">PMID:31604309</ref>. Heme b558 acts as the primary electron acceptor by catalyzing the [https://en.wikipedia.org/wiki/Hydroquinone#Redox oxidation of quinol]<ref name="Alexander">PMID:31723136</ref>. Conserved <scene name='83/832931/Met393/1'>His186 and Met393</scene> help to stabilize heme b558<ref name="Alexander">PMID:31723136</ref>. Heme b558 transfers the electrons to heme b595, which transfers them to the active site heme d<ref name= "Safarian">PMID:31604309</ref>. Multiple residues help stabilzie this electron trasnfer including a conserved <scene name='83/832931/Trp441/6'>Trp441</scene> that assists heme b595 in transferring electrons to heme d<ref name="Safarian2">PMID:27126043</ref>. A conserved <scene name='83/832931/Hemeb595/2'>Glu445</scene> is also essential for charge stabilization of heme b595<ref name="Alexander">PMID:31723136</ref>, while <scene name='83/832931/Hemeh19/3'>His19</scene> stabilizes heme d<ref name="Safarian2">PMID:27126043</ref>. As heme d collects the electrons from heme b595, <scene name='83/832931/Heme_d/3'>Glu99</scene> in the O-channel facilities the binding of oxygen to heme d, and <scene name='83/832931/Heme_d/3'>Ser108, Glu107, and Ser140</scene> in the h-channel facilitate proton transfer to heme d<ref name="Safarian">PMID:31604309</ref>. Similar to the three hemes, the <scene name='83/832931/Uq8/3'>ubiquinone-8</scene> (UQ-8) molecule found in CydB mimics the triangular formation to stabilize the subunit<ref name="Safarian">PMID:31604309</ref>.

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@@ Line 21: / Line 21: @@
 === H and O channels ===
 [[Image:O_AND_H_CHANNEL.png|300 px|right|thumb|'''Figure 3'''. H and o-channels of cytochrome bd-oxidase in ''E. coli''. Channels are outlined in gray, water is shown as spheres, and various amino acids are labeled above.  [[https://www.rcsb.org/structure/6RX4 PDB:6RX4]]]]
-The hydrogen and oxygen channels (Fig. 3) are essential for H<sup>+</sup> and O<sub>2</sub> molecules to reach the active site of cytochrome ''bd'' oxidase. A [https://en.wikipedia.org/wiki/Chemiosmosis#The_proton-motive_force proton motive force] generated by the oxidase<ref name= "Safarian">PMID:31604309</ref> allows protons from the cytoplasm to flow through a hydrophilic <scene name='83/832931/Overall_h_channel/2'>H-channel</scene> full of water (pink dots), entering at <scene name='83/832931/Start_of_h_channel/2'>Asp119<sup>A</sup></scene> and moving past <scene name='83/832931/Start_of_h_channel/2'>Lys57<sup>A</sup>, Lys109<sup>B</sup>, Asp105<sup>B</sup>, Tyr379<sup>B</sup>, and Asp58<sup>B</sup></scene><ref name="Alexander">PMID:31723136</ref> where they can be transferred to the active site with the help of the conserved residues <scene name='83/832931/End_of_h_channel/4'>Ser108<sup>A</sup>, Glu107<sup>A</sup>, and Ser140<sup>A</sup></scene><ref name= "Safarian">PMID:31604309</ref>.  A smaller <scene name='83/832931/O_channel_overall/3'>O-channel</scene> also exists that transitions from hydrophobic to hydrophilic as it gets closer to the active site. This channel allows oxygen to reach the active site, starting near <scene name='83/832931/Ochannel/2'>Trp63</scene> in CydB and passing by <scene name='83/832931/Ochannel/2'>Ile144<sup>A</sup>, Leu101<sup>A</sup>, and Glu99<sup>A</sup></scene><ref name= "Safarian">PMID:31604309</ref>, which assists with the binding of oxygen to the active site.  The o-channel channel is approximately 1.5 [https://en.wikipedia.org/wiki/Angstrom Å] in diameter<ref name="Alexander">PMID:31723136</ref>, which may help with [https://en.wikipedia.org/wiki/Chemical_specificity selectivity].
+The hydrogen and oxygen channels (Fig. 3) are essential for H<sup>+</sup> and O<sub>2</sub> molecules to reach the active site of cytochrome ''bd'' oxidase. A [https://en.wikipedia.org/wiki/Chemiosmosis#The_proton-motive_force proton motive force] generated by the oxidase<ref name= "Safarian">PMID:31604309</ref> allows protons from the cytoplasm to flow through a hydrophilic <scene name='83/832931/Overall_h_channel/2'>H-channel</scene> full of water (pink dots), entering at <scene name='83/832931/Start_of_h_channel/2'>Asp119<sup>A</sup></scene> and moving past <scene name='83/832931/Start_of_h_channel/2'>Lys57<sup>A</sup>, Lys109<sup>B</sup>, Asp105<sup>B</sup>, Tyr379<sup>B</sup>, and Asp58<sup>B</sup></scene><ref name="Alexander">PMID:31723136</ref> where they can be transferred to the active site with the help of the conserved residues <scene name='83/832931/End_of_h_channel/4'>Ser108<sup>A</sup>, Glu107<sup>A</sup>, and Ser140<sup>A</sup></scene><ref name= "Safarian">PMID:31604309</ref>.  A smaller <scene name='83/832931/O_channel_overall/3'>O-channel</scene> also exists that transitions from hydrophobic to hydrophilic as it gets closer to the active site. This channel allows oxygen to reach the active site, starting near <scene name='83/832931/Ochannel/2'>Trp63</scene> in CydB and passing by <scene name='83/832931/Ochannel/2'>Ile144<sup>A</sup>, Leu101<sup>A</sup>, and Glu99<sup>A</sup></scene><ref name= "Safarian">PMID:31604309</ref>, which assists with the binding of oxygen to the active site.  The O-channel channel is approximately 1.5 [https://en.wikipedia.org/wiki/Angstrom Å] in diameter<ref name="Alexander">PMID:31723136</ref>, which may help with [https://en.wikipedia.org/wiki/Chemical_specificity selectivity].
-Interestingly, the O-channel does not exist in the cytochrome ''bd'' oxidase of [https://www.rcsb.org/structure/5DOQ ''Geobacillus thermodenitrificans'']; instead, oxygen binds directly to the active site<ref name="Safarian2">PMID: 27126043</ref>.  The <scene name='83/832931/Cyds/1'>CydS</scene> subunit found in E. coli blocks this alternate oxygen entry site, which allows oxygen to travel through the O-channel<ref name="Safarian">PMID:31604309</ref><ref name="Alexander">PMID:31723136</ref>.  The presence of an o-channel affects oxidase activity, as the ''E. coli'' oxidase acts as a "true" oxidase, while the ''G. thermodenitrificans'' bd oxidase contributes more to detoxification<ref name="Alexander">PMID:31723136</ref>.
+Interestingly, the O-channel does not exist in the cytochrome ''bd'' oxidase of [https://www.rcsb.org/structure/5DOQ ''Geobacillus thermodenitrificans'']; instead, oxygen binds directly to the active site<ref name="Safarian2">PMID: 27126043</ref>.  The <scene name='83/832931/Cyds/1'>CydS</scene> subunit found in ''E. coli'' blocks this alternate oxygen entry site, which allows oxygen to travel through the O-channel<ref name="Safarian">PMID:31604309</ref><ref name="Alexander">PMID:31723136</ref>.  The presence of an O-channel affects oxidase activity, as the ''E. coli'' oxidase acts as a "true" oxidase, while the ''G. thermodenitrificans'' bd oxidase contributes more to detoxification<ref name="Alexander">PMID:31723136</ref>.
 === Hemes ===
 Three <scene name='83/832931/Heme/6'>hemes</scene> are present in the CydA subunit. These three hemes form a triangle to maximize subunit stability<ref name="Safarian">PMID:31604309</ref><ref name="Alexander">PMID:31723136</ref><ref name="Safarian2">PMID:27126043</ref>, which is an evolutionary conserved feature across bd oxidases<ref name="Safarian">PMID:31604309</ref>.  Heme b<sub>558</sub> acts as the primary electron acceptor by catalyzing the [https://en.wikipedia.org/wiki/Hydroquinone#Redox oxidation of quinol]<ref name="Alexander">PMID:31723136</ref>. Conserved <scene name='83/832931/Met393/1'>His186 and Met393</scene> help to stabilize heme b558<ref name="Alexander">PMID:31723136</ref>. Heme b<sub>558</sub> transfers the electrons to heme b595, which transfers them to the active site heme d<ref name= "Safarian">PMID:31604309</ref>.  Multiple residues help stabilzie this electron trasnfer including a conserved <scene name='83/832931/Trp441/6'>Trp441</scene> that assists heme b<sub>595</sub> in transferring electrons to heme d<ref name="Safarian2">PMID:27126043</ref>.  A conserved <scene name='83/832931/Hemeb595/2'>Glu445</scene> is also essential for charge stabilization of heme b<sub>595</sub><ref name="Alexander">PMID:31723136</ref>, while <scene name='83/832931/Hemeh19/3'>His19</scene> stabilizes heme d<ref name="Safarian2">PMID:27126043</ref>. As heme d collects the electrons from heme b<sub>595</sub>, <scene name='83/832931/Heme_d/3'>Glu99</scene> in the O-channel facilities the binding of oxygen to heme d, and <scene name='83/832931/Heme_d/3'>Ser108, Glu107, and Ser140</scene> in the h-channel facilitate proton transfer to heme d<ref name="Safarian">PMID:31604309</ref>. Similar to the three hemes, the <scene name='83/832931/Uq8/3'>ubiquinone-8</scene> (UQ-8) molecule found in CydB mimics the triangular formation to stabilize the subunit<ref name="Safarian">PMID:31604309</ref>.