Proteopedia - User contributions [en]

Cytochrome c

2011-04-09T00:14:46Z

Melissa Morrison:

{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Cytochrome_c/Cyt_c/1}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== ''Rhodothermus marinus'' cytochrome ''c'' ==

=== Structure ===

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main /> Cytochrome ''c'' has also been determined to be a major signalling molecule in the apoptotic pathways.

=== Electron transport chain ===

In the electron transport chain (ETC), cyt ''c'' shuttles electrons between the respiratory complexes III and IV; complex III is the cytochrome ''bc''1 complex and IV is cyt ''c'' oxidase. Initially, the heme iron in cyt ''c'' is in the reduced, Fe3+ state; this allows for the uptake of one electron, oxidizing the iron to the Fe2+ state.<ref name='etc'>Karp, Gerald (2008). Cell and Molecular Biology (5th edition). Hoboken, NJ: John Wiley & Sons. ISBN 978-0470042175.</ref> The ETC in eukaryotes is quite simple compared to that of prokaryotes (Figure 3). [[Image:Etc.gif |frame|left| |size|300| Figure 3. The electron transport chain of a) eukaryotes as compared to b) prokaryotes.]] In prokaryotic systems, electrons can enter the ETC at a number of places and multiple donors can be in play; however, the underlying transport system remains the same. Electrons are ultimately transferred from donor to various redox complexes including the ''bc''1 complex and cytochrome ''c'', and finally to a terminal electron acceptor such as molecular oxygen in eukaryotes.<ref name=etc />

The cytochrome oxidase reaction accounts for nearly 90% of all oxygen uptake in most cells.<ref name=etc /> Due to the large role of cytochromes within the ETC, it would be highly detrimental to the cell if any inhibitors were to be present in the organism. Cyanide and azide bind tightly to the cytochrome oxidase complex, halting electron transport and reducing the overall ATP production.<ref name=etc />

=== Apoptosis ===

In all organisms, cells undergo [http://en.wikipedia.org/wiki/Apoptosis apoptosis], or programmed cell death, by which there is an extrinsic and an intrinsic pathway. The extrinsic pathway involves an immune response by killer lymphocytes, and once the lymphocyte has been bound to the target cell, an apoptotic cascade occurs.<ref name=etc /> The intrinsic pathway includes cyt ''c'', present in the intermembrane space of mitochondria. In this pathway, the presence of an apoptotic stimulus causes cyt ''c'' to be released into the cytosol. Cytochrome ''c'' in the cytosol now can be recognized and bound to various apoptotic factors, activating them and forming the [http://en.wikipedia.org/wiki/Apoptosome apoptosome]. The apoptosome recruits [http://en.wikipedia.org/wiki/Caspase caspases], which are activated and result in a caspase cascade to proceed with apoptosis.<ref name=etc />

Cytochrome ''c'' is required for the intrinsic apoptotic process to function properly. Such as with the electron transport chain, a mutation affecting cyt ''c'' or other structures in apoptosis could cause either an increase or a decrease in the rate of apoptosis.

== References ==

<references/>

Cytochrome c

2011-04-09T00:08:53Z

Melissa Morrison:

{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== ''Rhodothermus marinus'' cytochrome ''c'' ==

=== Structure ===

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main /> Cytochrome ''c'' has also been determined to be a major signalling molecule in the apoptotic pathways.

=== Electron transport chain ===

In the electron transport chain (ETC), cyt ''c'' shuttles electrons between the respiratory complexes III and IV; complex III is the cytochrome ''bc''1 complex and IV is cyt ''c'' oxidase. Initially, the heme iron in cyt ''c'' is in the reduced, Fe3+ state; this allows for the uptake of one electron, oxidizing the iron to the Fe2+ state.<ref name='etc'>Karp, Gerald (2008). Cell and Molecular Biology (5th edition). Hoboken, NJ: John Wiley & Sons. ISBN 978-0470042175.</ref> The ETC in eukaryotes is quite simple compared to that of prokaryotes (Figure 3). [[Image:Etc.gif |frame|left| |size|300| Figure 3. The electron transport chain of a) eukaryotes as compared to b) prokaryotes.]] In prokaryotic systems, electrons can enter the ETC at a number of places and multiple donors can be in play; however, the underlying transport system remains the same. Electrons are ultimately transferred from donor to various redox complexes including the ''bc''1 complex and cytochrome ''c'', and finally to a terminal electron acceptor such as molecular oxygen in eukaryotes.<ref name=etc />

The cytochrome oxidase reaction accounts for nearly 90% of all oxygen uptake in most cells.<ref name=etc /> Due to the large role of cytochromes within the ETC, it would be highly detrimental to the cell if any inhibitors were to be present in the organism. Cyanide and azide bind tightly to the cytochrome oxidase complex, halting electron transport and reducing the overall ATP production.<ref name=etc />

=== Apoptosis ===

In all organisms, cells undergo [http://en.wikipedia.org/wiki/Apoptosis apoptosis], or programmed cell death, by which there is an extrinsic and an intrinsic pathway. The extrinsic pathway involves an immune response by killer lymphocytes, and once the lymphocyte has been bound to the target cell, an apoptotic cascade occurs.<ref name=etc /> The intrinsic pathway includes cyt ''c'', present in the intermembrane space of mitochondria. In this pathway, the presence of an apoptotic stimulus causes cyt ''c'' to be released into the cytosol. Cytochrome ''c'' in the cytosol now can be recognized and bound to various apoptotic factors, activating them and forming the [http://en.wikipedia.org/wiki/Apoptosome apoptosome]. The apoptosome recruits [http://en.wikipedia.org/wiki/Caspase caspases], which are activated and result in a caspase cascade to proceed with apoptosis.<ref name=etc />

Cytochrome ''c'' is required for the intrinsic apoptotic process to function properly. Such as with the electron transport chain, a mutation affecting cyt ''c'' or other structures in apoptosis could cause either an increase or a decrease in the rate of apoptosis.

== References ==

<references/>

Cytochrome c

2011-04-09T00:08:25Z

Melissa Morrison: New page:  {{Template:Sandbox_Reserved_BCMB307}}  {{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/C...

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== ''Rhodothermus marinus'' cytochrome ''c'' ==

=== Structure ===

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main /> Cytochrome ''c'' has also been determined to be a major signalling molecule in the apoptotic pathways.

=== Electron transport chain ===

In the electron transport chain (ETC), cyt ''c'' shuttles electrons between the respiratory complexes III and IV; complex III is the cytochrome ''bc''1 complex and IV is cyt ''c'' oxidase. Initially, the heme iron in cyt ''c'' is in the reduced, Fe3+ state; this allows for the uptake of one electron, oxidizing the iron to the Fe2+ state.<ref name='etc'>Karp, Gerald (2008). Cell and Molecular Biology (5th edition). Hoboken, NJ: John Wiley & Sons. ISBN 978-0470042175.</ref> The ETC in eukaryotes is quite simple compared to that of prokaryotes (Figure 3). [[Image:Etc.gif |frame|left| |size|300| Figure 3. The electron transport chain of a) eukaryotes as compared to b) prokaryotes.]] In prokaryotic systems, electrons can enter the ETC at a number of places and multiple donors can be in play; however, the underlying transport system remains the same. Electrons are ultimately transferred from donor to various redox complexes including the ''bc''1 complex and cytochrome ''c'', and finally to a terminal electron acceptor such as molecular oxygen in eukaryotes.<ref name=etc />

The cytochrome oxidase reaction accounts for nearly 90% of all oxygen uptake in most cells.<ref name=etc /> Due to the large role of cytochromes within the ETC, it would be highly detrimental to the cell if any inhibitors were to be present in the organism. Cyanide and azide bind tightly to the cytochrome oxidase complex, halting electron transport and reducing the overall ATP production.<ref name=etc />

=== Apoptosis ===

In all organisms, cells undergo [http://en.wikipedia.org/wiki/Apoptosis apoptosis], or programmed cell death, by which there is an extrinsic and an intrinsic pathway. The extrinsic pathway involves an immune response by killer lymphocytes, and once the lymphocyte has been bound to the target cell, an apoptotic cascade occurs.<ref name=etc /> The intrinsic pathway includes cyt ''c'', present in the intermembrane space of mitochondria. In this pathway, the presence of an apoptotic stimulus causes cyt ''c'' to be released into the cytosol. Cytochrome ''c'' in the cytosol now can be recognized and bound to various apoptotic factors, activating them and forming the [http://en.wikipedia.org/wiki/Apoptosome apoptosome]. The apoptosome recruits [http://en.wikipedia.org/wiki/Caspase caspases], which are activated and result in a caspase cascade to proceed with apoptosis.<ref name=etc />

Cytochrome ''c'' is required for the intrinsic apoptotic process to function properly. Such as with the electron transport chain, a mutation affecting cyt ''c'' or other structures in apoptosis could cause either an increase or a decrease in the rate of apoptosis.

== References ==

<references/>

File:Etc.gif

2011-04-05T00:11:56Z

Melissa Morrison: uploaded a new version of "Image:Etc.gif"

== Summary ==
Electron transport chain of eukaryotes vs. prokaryotes.
== Licensing ==
{{PD-self}}

File:Etc.gif

2011-04-04T14:03:15Z

Melissa Morrison: uploaded a new version of "Image:Etc.gif": Electron transport chain of a) eukaryotes vs. b) prokaryotes.

== Summary ==
Electron transport chain of eukaryotes vs. prokaryotes.
== Licensing ==
{{PD-self}}

File:Etc.gif

2011-04-04T14:02:03Z

Melissa Morrison: uploaded a new version of "Image:Etc.gif": Electron transport chain of a) eukaryotes vs b) prokaryotes.

== Summary ==
Electron transport chain of eukaryotes vs. prokaryotes.
== Licensing ==
{{PD-self}}

File:Etc.gif

2011-04-04T13:59:42Z

Melissa Morrison: Electron transport chain of eukaryotes vs. prokaryotes.

== Summary ==
Electron transport chain of eukaryotes vs. prokaryotes.
== Licensing ==
{{PD-self}}

Sandbox Reserved 335

2011-04-04T13:57:28Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== ''Rhodothermus marinus'' cytochrome ''c'' ==

=== Structure ===

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain (ETC), cyt ''c'' shuttles electrons between the respiratory complexes III and IV; complex III is the cytochrome ''bc''1 complex and IV is cyt ''c'' oxidase. Initially, the heme iron in cyt ''c'' is in the reduced, Fe3+ state; this allows for the uptake of one electron, oxidizing the iron to the Fe2+ state.<ref name='etc'>ISBN:10-0-470-04217-6</ref> The ETC in eukaryotes is quite simple compared to that of prokaryotes.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.<ref name=apop>doi:10.1038/ng.103</ref>

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T13:44:00Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== ''Rhodothermus marinus'' cytochrome ''c'' ==

=== Structure ===

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt ''c'' shuttles electrons between the respiratory complexes III and IV. Initially, the heme iron is in the reduced, Fe3+ state; this allows for the uptake of one electron, oxidizing the iron to the Fe2+ state.<ref name='etc'>ISBN:10-0-470-04217-6</ref>

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.<ref name=apop>doi:10.1038/ng.103</ref>

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T13:32:50Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== ''Rhodothermus marinus'' cytochrome ''c'' ==

=== Structure ===

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt ''c'' shuttles electrons between the respiratory complexes III and IV. Initially, the heme iron is in the reduced, Fe3+ state; this allows for the uptake of one electron, oxidizing the iron to the Fe2+ state.<ref name='etc'>ISBN:10-0-470-04217-6.</ref>

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.<ref name=apop>doi:10.1038/ng.103</ref>

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T13:18:21Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== ''Rhodothermus marinus'' cytochrome ''c'' ==

=== Structure ===

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt ''c'' shuttles electrons between the respiratory complexes III and IV. Initially, the heme iron is in the reduced, Fe3+ state; this allows for the uptake of one electron, oxidizing the iron to the Fe2+ state.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.<ref name=apop>doi:10.1038/ng.103</ref>

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T13:11:18Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== ''Rhodothermus marinus'' cytochrome ''c'' ==

=== Structure ===

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.<ref name=apop>doi:10.1038/ng.103</ref>

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T10:37:27Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== ''Rhodothermus marinus'' cytochrome ''c'' ==

=== Structure ===

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T10:35:25Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T10:35:05Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.<ref name=apoptosis>doi:10.1038/ng.103</ref>

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T10:33:15Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure.

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T10:22:45Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> A final thing to note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T10:18:38Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'' and ''b'' contain heme ''a'' and ''b'', respectively, and cyt ''d'' '''contains a tetrapyrrolic chelate of iron'''.<ref name="cytd">MeSH [http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Cytochrome+d Cytochrome ''d'']</ref> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> A final thing to note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.<ref name='apoptosis'>doi:10.1038/ng.103</ref>

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T10:18:16Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'' and ''b'' contain heme ''a'' and ''b'', respectively, and cyt ''d'' '''contains a tetrapyrrolic chelate of iron'''.<ref name="cytd">MeSH [http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Cytochrome+d Cytochrome ''d'']</ref> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> A final thing to note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.<ref name=apop>doi:10.1038/ng.103</ref>

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T10:17:46Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'' and ''b'' contain heme ''a'' and ''b'', respectively, and cyt ''d'' '''contains a tetrapyrrolic chelate of iron'''.<ref name="cytd">MeSH [http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Cytochrome+d Cytochrome ''d'']</ref> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> A final thing to note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T10:16:31Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'' and ''b'' contain heme ''a'' and ''b'', respectively, and cyt ''d'' '''contains a tetrapyrrolic chelate of iron'''.<ref name="cytd">MeSH [http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Cytochrome+d Cytochrome ''d'']</ref> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> A final thing to note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are required for the apoptotic and electron transfer processes to function properly. <ref name=apop>doi:10.1038/ng.103</ref>

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T10:11:58Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'' and ''b'' contain heme ''a'' and ''b'', respectively, and cyt ''d'' '''contains a tetrapyrrolic chelate of iron'''.<ref name="cytd">MeSH [http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Cytochrome+d Cytochrome ''d'']</ref> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> A final thing to note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Electron transport chain ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

=== Apoptosis ===

== Importance ==

C-type cytochromes are

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T09:45:20Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'' and ''b'' contain heme ''a'' and ''b'', respectively, and cyt ''d'' '''contains a tetrapyrrolic chelate of iron'''.<ref name="cytd">MeSH [http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Cytochrome+d Cytochrome ''d'']</ref> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> A final thing to note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to also contain a coordinated sulfate ion; this ion has been seen to mediate crystal contact between neighbouring protein molecules. The carboxylate oxygen of Glu122, when protonated, was also found to be involved in hydrogen bonding with this sulfate ion.<ref name=main />

The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''.

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes, or their analogs, in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] to heme-copper oxygen reductases (HCOs) during [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in the electron transport systems in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Mechanism ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

== Importance ==

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T09:37:56Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'' and ''b'' contain heme ''a'' and ''b'', respectively, and cyt ''d'' '''contains a tetrapyrrolic chelate of iron'''.<ref name="cytd">MeSH [http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Cytochrome+d Cytochrome ''d'']</ref> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> A final thing to note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to also contain a coordinated sulfate ion; this ion has been seen to mediate crystal contact between neighbouring protein molecules. The carboxylate oxygen of Glu122, when protonated, was also found to be involved in hydrogen bonding with this sulfate ion.<ref name=main />

The observation of these structural motifs in C-type cytochromes other than that of ''R. marinus'', has brought attention to the fact that this could support divergent evolution of cytochromes ''c''.<ref name=main /> These motifs have been present in a number of different bacteria and have been seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs have not been observed in other bacterial phyla.<ref name=main />

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes, or their analogs, in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] to heme-copper oxygen reductases (HCOs) during [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in the electron transport systems in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Mechanism ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

== Importance ==

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T09:10:15Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'' and ''b'' contain heme ''a'' and ''b'', respectively, and cyt ''d'' '''contains a tetrapyrrolic chelate of iron'''.<ref name="cytd">MeSH [http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Cytochrome+d Cytochrome ''d'']</ref> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

=== Secondary Structure ===

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> A final thing to note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to also contain a coordinated sulfate ion; this ion has been seen to mediate crystal contact between neighbouring protein molecules. The carboxylate oxygen of Glu122, when protonated, was also found to be involved in hydrogen bonding with this sulfate ion.<ref name=main />

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes, or their analogs, in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] to heme-copper oxygen reductases (HCOs) during [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in the electron transport systems in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Mechanism ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

== Importance ==

== References ==

<references/>

Sandbox Reserved 335

2011-04-04T09:04:58Z

Melissa Morrison:

{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'' and ''b'' contain heme ''a'' and ''b'', respectively, and cyt ''d'' '''contains a tetrapyrrolic chelate of iron'''.<ref name="cytd">MeSH [http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Cytochrome+d Cytochrome ''d'']</ref> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

=== Secondary Structure ===

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> A final thing to note is the number of methionine residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the lower front side of the heme.<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to also contain a coordinated sulfate ion; this ion has been seen to mediate crystal contact between neighbouring protein molecules. The carboxylate oxygen of Glu122, when protonated, was also found to be involved in hydrogen bonding with this sulfate ion.<ref name=main />

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes, or their analogs, in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] to heme-copper oxygen reductases (HCOs) during [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in the electron transport systems in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Mechanism ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

== Importance ==

== References ==

<references/>

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{{Template:Sandbox_Reserved_BCMB307}}


{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}}

The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution.

== Introduction ==

[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'' and ''b'' contain heme ''a'' and ''b'', respectively, and cyt ''d'' '''contains a tetrapyrrolic chelate of iron'''.<ref name="cytd">MeSH [http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Cytochrome+d Cytochrome ''d'']</ref> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme />

Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref>

== Structure ==

<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' />

All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where a histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', '''XX represents a threonine (Thr46) and an alanine residue (Ala47); these two residues are not involved in coordinating the iron ligand.'''

[[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl covalently attached to Cys 45, and R3 is a methyl covalently attached to Cys48.]]

=== Secondary Structure ===

The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wrap around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''2 as well as mitochondrial cyt ''c'', a similar yet shorter helix such as helix B' was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main />

As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to also contain a coordinated sulfate ion; this ion has been seen to mediate crystal contact between neighbouring protein molecules. The carboxylate oxygen of Glu122, when protonated, was also found to be involved in hydrogen bonding with this sulfate ion.<ref name=main />

== Function ==

Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''1 complexes, or their analogs, in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] to heme-copper oxygen reductases (HCOs) during [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''3 oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O2 to water.<ref>PMID:11334784</ref> In addition to being involved in the electron transport systems in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main />

In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is

=== Mechanism ===

In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV.

== Importance ==

== References ==

<references/>

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Melissa Morrison: The tetrapyrrolic heme prosthetic group involved in chelating many different proteins, such as hemoglobin, myoglobin, and cytochromes.

== Summary ==
The tetrapyrrolic heme prosthetic group involved in chelating many different proteins, such as hemoglobin, myoglobin, and cytochromes.
== Licensing ==
{{PD-self}}

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