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Hemeproteins
From Proteopedia
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<StructureSection load='Cytc6.pdb' size='400' side='right' scene='82/828363/Cv/1' caption=''> | <StructureSection load='Cytc6.pdb' size='400' side='right' scene='82/828363/Cv/1' caption=''> | ||
| - | =Cytochromes= | + | ==Cytochromes== |
==Cytochrome b5== | ==Cytochrome b5== | ||
'''Cytochrome b5''' (CB) functions as an electron transport carrier for several membrane-bound oxygenases. <scene name='49/490878/Cv/2'>CB is heme-containing protein</scene>. The microsomal and mitochondrial CB are membrane-bound while bacterial and other animal tissue CB are soluble. '''Cytochrome b562''' is the the b-type cytochrome from ''E. coli''.<ref>PMID:12559387</ref> | '''Cytochrome b5''' (CB) functions as an electron transport carrier for several membrane-bound oxygenases. <scene name='49/490878/Cv/2'>CB is heme-containing protein</scene>. The microsomal and mitochondrial CB are membrane-bound while bacterial and other animal tissue CB are soluble. '''Cytochrome b562''' is the the b-type cytochrome from ''E. coli''.<ref>PMID:12559387</ref> | ||
==Cytochrome c== | ==Cytochrome c== | ||
| - | ==Structural and kinetic studies of imidazole binding to two members of the cytochrome c6 family reveal an important role for a conserved heme pocket residue<ref>DOI 10.1007/s00775-011-0758-y</ref>== | + | ===Structural and kinetic studies of imidazole binding to two members of the cytochrome c6 family reveal an important role for a conserved heme pocket residue<ref>DOI 10.1007/s00775-011-0758-y</ref>=== |
<scene name='Journal:JBIC:7/Cv/4'>Cytochrome c6</scene> is a member of the class I family of c-type cytochromes with a distinctive <scene name='Journal:JBIC:7/Cv/5'>α-helical fold</scene> and a <scene name='Journal:JBIC:7/Cv/6'>methionine and histidine residue serving as axial heme iron ligands</scene>. They function in the photosynthetic electron transport chain of cyanobacteria where they shuttle an electron from the cytochrome b6f complex to photosystem I. Structures of numerous cytochrome ''c''<sub>6</sub> proteins have been determined and all have the <scene name='Journal:JBIC:7/Cv/7'>methionine ligand coordinating to the iron</scene>. In the present work we have solved the structure of the '''Q51V''' site-directed variant of ''Phormidium laminosum'' cytochrome ''c''<sub>6</sub>. This project is part of a study that is aimed at gaining insight into protein factors which modulate the heme mid-point redox potential in the cytochrome ''c''<sub>6</sub> family. The '''Q51V''' variant has been shown to tune over 100 mV of heme redox potential, which for a single heme pocket mutation is very significant and has consequences for function. | <scene name='Journal:JBIC:7/Cv/4'>Cytochrome c6</scene> is a member of the class I family of c-type cytochromes with a distinctive <scene name='Journal:JBIC:7/Cv/5'>α-helical fold</scene> and a <scene name='Journal:JBIC:7/Cv/6'>methionine and histidine residue serving as axial heme iron ligands</scene>. They function in the photosynthetic electron transport chain of cyanobacteria where they shuttle an electron from the cytochrome b6f complex to photosystem I. Structures of numerous cytochrome ''c''<sub>6</sub> proteins have been determined and all have the <scene name='Journal:JBIC:7/Cv/7'>methionine ligand coordinating to the iron</scene>. In the present work we have solved the structure of the '''Q51V''' site-directed variant of ''Phormidium laminosum'' cytochrome ''c''<sub>6</sub>. This project is part of a study that is aimed at gaining insight into protein factors which modulate the heme mid-point redox potential in the cytochrome ''c''<sub>6</sub> family. The '''Q51V''' variant has been shown to tune over 100 mV of heme redox potential, which for a single heme pocket mutation is very significant and has consequences for function. | ||
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Protein (un)folding studies on cytochrome c have revealed that (un)folding involves structural units called 'foldons'. The regions in the Q51V imidazole-adduct where structural changes occur map well to the two foldons predicted to unfold first in cytochrome c. Thus <scene name='Journal:JBIC:7/Cv/14'>imidazole triggers the release of the methionine ligand in the Q51V variant</scene>, leading to the formation of an early unfolding intermediate that is stabilised by <scene name='Journal:JBIC:7/Cv/15'>imidazole binding to the vacant heme iron coordination position</scene>, enabling it to be captured in the crystalline form. | Protein (un)folding studies on cytochrome c have revealed that (un)folding involves structural units called 'foldons'. The regions in the Q51V imidazole-adduct where structural changes occur map well to the two foldons predicted to unfold first in cytochrome c. Thus <scene name='Journal:JBIC:7/Cv/14'>imidazole triggers the release of the methionine ligand in the Q51V variant</scene>, leading to the formation of an early unfolding intermediate that is stabilised by <scene name='Journal:JBIC:7/Cv/15'>imidazole binding to the vacant heme iron coordination position</scene>, enabling it to be captured in the crystalline form. | ||
| - | ==Structural model of the [Fe]-hydrogenase/cytochrome C553 complex combining NMR and soft-docking<ref>PMID:10748163</ref>== | + | ===Structural model of the [Fe]-hydrogenase/cytochrome C553 complex combining NMR and soft-docking<ref>PMID:10748163</ref>=== |
The <scene name='1e08/1e08-cofactors/1'>complex</scene> shows the specific interaction of the hydrogenase (light blue) with the cytochrome (pink), revealing the path of electron transport from the <scene name='1e08/1e08-activecluster/3'>active site metal cluster</scene>, through three iron-sulfur clusters, and ending in the cytochrome heme (colored red). Two <scene name='1e08/1e08-cys/2'>cysteine amino acids at the interface</scene>, CYS 38 in the hydrogenase and CYS10 in the cytochrome, are thought to provide the electron transfer pathway between the two proteins (these scenes were created by Jaime Prilusky, David S. Goodsell, and Eran Hodis). | The <scene name='1e08/1e08-cofactors/1'>complex</scene> shows the specific interaction of the hydrogenase (light blue) with the cytochrome (pink), revealing the path of electron transport from the <scene name='1e08/1e08-activecluster/3'>active site metal cluster</scene>, through three iron-sulfur clusters, and ending in the cytochrome heme (colored red). Two <scene name='1e08/1e08-cys/2'>cysteine amino acids at the interface</scene>, CYS 38 in the hydrogenase and CYS10 in the cytochrome, are thought to provide the electron transfer pathway between the two proteins (these scenes were created by Jaime Prilusky, David S. Goodsell, and Eran Hodis). | ||
| - | == Conformational control of the binding of diatomic gases to cytochrome c’ <ref>PMID 25792378 </ref>== | + | === Conformational control of the binding of diatomic gases to cytochrome c’ <ref>PMID 25792378 </ref>=== |
The cytochromes c′ (CYTcp) are found in denitrifying, methanotrophic and photosynthetic bacteria. These proteins are able to form stable adducts with CO and NO but not with O2. The binding of NO to CYTcp currently provides the best structural model for the NO activation mechanism of soluble guanylate cyclase. Ligand binding in CYTcps has been shown to be highly dependent on residues in both the proximal and distal heme pockets. Group 1 CYTcps typically have a phenylalanine residue positioned close to the distal face of heme, while for group 2, this residue is typically leucine. We have structurally, spectroscopically and kinetically characterised the CYTcp from ''Shewanella frigidimarina'' <scene name='69/696899/Cv/2'>(SFCP)</scene>, a protein that has a distal phenylalanine residue and a lysine in the proximal pocket in place of the more common arginine (<font color='red'><b>monomer A is colored in red</b></font>, <span style="color:lime;background-color:black;font-weight:bold;">monomer B in green</span>, and <span style="color:yellow;background-color:black;font-weight:bold;">heme group in yellow</span>). <scene name='69/696899/Cv/3'>Each monomer of the SFCP dimer folds as a 4-alpha-helical bundle</scene> in a similar manner to CYTcps previously characterised. | The cytochromes c′ (CYTcp) are found in denitrifying, methanotrophic and photosynthetic bacteria. These proteins are able to form stable adducts with CO and NO but not with O2. The binding of NO to CYTcp currently provides the best structural model for the NO activation mechanism of soluble guanylate cyclase. Ligand binding in CYTcps has been shown to be highly dependent on residues in both the proximal and distal heme pockets. Group 1 CYTcps typically have a phenylalanine residue positioned close to the distal face of heme, while for group 2, this residue is typically leucine. We have structurally, spectroscopically and kinetically characterised the CYTcp from ''Shewanella frigidimarina'' <scene name='69/696899/Cv/2'>(SFCP)</scene>, a protein that has a distal phenylalanine residue and a lysine in the proximal pocket in place of the more common arginine (<font color='red'><b>monomer A is colored in red</b></font>, <span style="color:lime;background-color:black;font-weight:bold;">monomer B in green</span>, and <span style="color:yellow;background-color:black;font-weight:bold;">heme group in yellow</span>). <scene name='69/696899/Cv/3'>Each monomer of the SFCP dimer folds as a 4-alpha-helical bundle</scene> in a similar manner to CYTcps previously characterised. | ||
Revision as of 13:07, 31 October 2019
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References
- ↑ Schenkman JB, Jansson I. The many roles of cytochrome b5. Pharmacol Ther. 2003 Feb;97(2):139-52. PMID:12559387
- ↑ Rajagopal BS, Wilson MT, Bendall DS, Howe CJ, Worrall JA. Structural and kinetic studies of imidazole binding to two members of the cytochrome c (6) family reveal an important role for a conserved heme pocket residue. J Biol Inorg Chem. 2011 Jan 26. PMID:21267610 doi:10.1007/s00775-011-0758-y
- ↑ Morelli X, Czjzek M, Hatchikian CE, Bornet O, Fontecilla-Camps JC, Palma NP, Moura JJ, Guerlesquin F. Structural model of the Fe-hydrogenase/cytochrome c553 complex combining transverse relaxation-optimized spectroscopy experiments and soft docking calculations. J Biol Chem. 2000 Jul 28;275(30):23204-10. PMID:10748163 doi:10.1074/jbc.M909835199
- ↑ Manole A, Kekilli D, Svistunenko DA, Wilson MT, Dobbin PS, Hough MA. Conformational control of the binding of diatomic gases to cytochrome c'. J Biol Inorg Chem. 2015 Mar 20. PMID:25792378 doi:http://dx.doi.org/10.1007/s00775-015-1253-7
