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- | [[Image:3u2m.jpg|left|200px]] | |
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- | <!-- | + | ==Crystal structure of human ALR mutant C142/145S== |
- | The line below this paragraph, containing "STRUCTURE_3u2m", creates the "Structure Box" on the page.
| + | <StructureSection load='3u2m' size='340' side='right'caption='[[3u2m]], [[Resolution|resolution]] 2.00Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | + | <table><tr><td colspan='2'>[[3u2m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U2M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U2M FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
- | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> |
- | {{STRUCTURE_3u2m| PDB=3u2m | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3u2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u2m OCA], [https://pdbe.org/3u2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u2m RCSB], [https://www.ebi.ac.uk/pdbsum/3u2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u2m ProSAT]</span></td></tr> |
| + | </table> |
| + | == Disease == |
| + | [https://www.uniprot.org/uniprot/ALR_HUMAN ALR_HUMAN] Congenital cataract - progressive muscular hypotonia - hearing loss - developmental delay. The disease is caused by mutations affecting the gene represented in this entry. |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/ALR_HUMAN ALR_HUMAN] Isoform 1: FAD-dependent sulfhydryl oxidase that regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen.<ref>PMID:19397338</ref> <ref>PMID:23186364</ref> <ref>PMID:20593814</ref> <ref>PMID:21383138</ref> <ref>PMID:22224850</ref> Isoform 2: May act as an autocrine hepatotrophic growth factor promoting liver regeneration.<ref>PMID:19397338</ref> <ref>PMID:23186364</ref> <ref>PMID:20593814</ref> <ref>PMID:21383138</ref> <ref>PMID:22224850</ref> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | The oxidative folding mechanism in the intermembrane space of human mitochondria underpins a disulfide relay system consisting of the import receptor Mia40 and the homodimeric FAD-dependent thiol oxidase ALR. The flavoprotein ALR receives two electrons per subunit from Mia40, which are then donated through one-electron reactions to two cytochrome c molecules, thus mediating a switch from two-electron to one-electron transfer. We dissect here the mechanism of the electron flux within ALR, characterizing at the atomic level the ALR intermediates that allow electrons to rapidly flow to cytochrome c. The intermediate critical for the electron-transfer process implies the formation of a specific inter-subunit disulfide which exclusively allows electron flow from Mia40 to FAD. This finding allows us to present a complete model for the electron-transfer pathway in ALR. |
| | | |
- | ===Crystal structure of human ALR mutant C142/145S===
| + | An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR.,Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Tokatlidis K J Am Chem Soc. 2012 Jan 25;134(3):1442-5. Epub 2012 Jan 6. PMID:22224850<ref>PMID:22224850</ref> |
| | | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> |
| + | <div class="pdbe-citations 3u2m" style="background-color:#fffaf0;"></div> |
| | | |
- | <!--
| + | ==See Also== |
- | The line below this paragraph, {{ABSTRACT_PUBMED_22224850}}, adds the Publication Abstract to the page
| + | *[[Sulfhydryl oxidase 3D structures|Sulfhydryl oxidase 3D structures]] |
- | (as it appears on PubMed at http://www.pubmed.gov), where 22224850 is the PubMed ID number.
| + | == References == |
- | -->
| + | <references/> |
- | {{ABSTRACT_PUBMED_22224850}}
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure== | + | |
- | [[3u2m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U2M OCA]. | + | |
- | | + | |
- | ==Reference== | + | |
- | <ref group="xtra">PMID:022224850</ref><ref group="xtra">PMID:021383138</ref><references group="xtra"/> | + | |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
- | [[Category: Thiol oxidase]] | + | [[Category: Large Structures]] |
- | [[Category: Banci, L.]] | + | [[Category: Banci L]] |
- | [[Category: Bertini, I.]] | + | [[Category: Bertini I]] |
- | [[Category: Calderone, V.]] | + | [[Category: Calderone V]] |
- | [[Category: Cefaro, C.]] | + | [[Category: Cefaro C]] |
- | [[Category: Ciofi-Baffoni, S.]] | + | [[Category: Ciofi-Baffoni S]] |
- | [[Category: Gallo, A.]] | + | [[Category: Gallo A]] |
- | [[Category: Alr]]
| + | |
- | [[Category: Fad]]
| + | |
- | [[Category: Flavin]]
| + | |
- | [[Category: Flavoprotein]]
| + | |
- | [[Category: Sulfhydryl oxidase]]
| + | |
| Structural highlights
Disease
ALR_HUMAN Congenital cataract - progressive muscular hypotonia - hearing loss - developmental delay. The disease is caused by mutations affecting the gene represented in this entry.
Function
ALR_HUMAN Isoform 1: FAD-dependent sulfhydryl oxidase that regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen.[1] [2] [3] [4] [5] Isoform 2: May act as an autocrine hepatotrophic growth factor promoting liver regeneration.[6] [7] [8] [9] [10]
Publication Abstract from PubMed
The oxidative folding mechanism in the intermembrane space of human mitochondria underpins a disulfide relay system consisting of the import receptor Mia40 and the homodimeric FAD-dependent thiol oxidase ALR. The flavoprotein ALR receives two electrons per subunit from Mia40, which are then donated through one-electron reactions to two cytochrome c molecules, thus mediating a switch from two-electron to one-electron transfer. We dissect here the mechanism of the electron flux within ALR, characterizing at the atomic level the ALR intermediates that allow electrons to rapidly flow to cytochrome c. The intermediate critical for the electron-transfer process implies the formation of a specific inter-subunit disulfide which exclusively allows electron flow from Mia40 to FAD. This finding allows us to present a complete model for the electron-transfer pathway in ALR.
An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR.,Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Tokatlidis K J Am Chem Soc. 2012 Jan 25;134(3):1442-5. Epub 2012 Jan 6. PMID:22224850[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Daithankar VN, Farrell SR, Thorpe C. Augmenter of liver regeneration: substrate specificity of a flavin-dependent oxidoreductase from the mitochondrial intermembrane space. Biochemistry. 2009 Jun 9;48(22):4828-37. doi: 10.1021/bi900347v. PMID:19397338 doi:http://dx.doi.org/10.1021/bi900347v
- ↑ Sztolsztener ME, Brewinska A, Guiard B, Chacinska A. Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. Traffic. 2013 Mar;14(3):309-20. doi: 10.1111/tra.12030. Epub 2012 Dec 16. PMID:23186364 doi:http://dx.doi.org/10.1111/tra.12030
- ↑ Daithankar VN, Schaefer SA, Dong M, Bahnson BJ, Thorpe C. Structure of the human sulfhydryl oxidase augmenter of liver regeneration and characterization of a human mutation causing an autosomal recessive myopathy. Biochemistry. 2010 Jul 1. PMID:20593814 doi:10.1021/bi100912m
- ↑ Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Kallergi E, Lionaki E, Pozidis C, Tokatlidis K. Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4811-6. Epub 2011 Mar 7. PMID:21383138 doi:10.1073/pnas.1014542108
- ↑ Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Tokatlidis K. An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR. J Am Chem Soc. 2012 Jan 25;134(3):1442-5. Epub 2012 Jan 6. PMID:22224850 doi:10.1021/ja209881f
- ↑ Daithankar VN, Farrell SR, Thorpe C. Augmenter of liver regeneration: substrate specificity of a flavin-dependent oxidoreductase from the mitochondrial intermembrane space. Biochemistry. 2009 Jun 9;48(22):4828-37. doi: 10.1021/bi900347v. PMID:19397338 doi:http://dx.doi.org/10.1021/bi900347v
- ↑ Sztolsztener ME, Brewinska A, Guiard B, Chacinska A. Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. Traffic. 2013 Mar;14(3):309-20. doi: 10.1111/tra.12030. Epub 2012 Dec 16. PMID:23186364 doi:http://dx.doi.org/10.1111/tra.12030
- ↑ Daithankar VN, Schaefer SA, Dong M, Bahnson BJ, Thorpe C. Structure of the human sulfhydryl oxidase augmenter of liver regeneration and characterization of a human mutation causing an autosomal recessive myopathy. Biochemistry. 2010 Jul 1. PMID:20593814 doi:10.1021/bi100912m
- ↑ Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Kallergi E, Lionaki E, Pozidis C, Tokatlidis K. Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4811-6. Epub 2011 Mar 7. PMID:21383138 doi:10.1073/pnas.1014542108
- ↑ Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Tokatlidis K. An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR. J Am Chem Soc. 2012 Jan 25;134(3):1442-5. Epub 2012 Jan 6. PMID:22224850 doi:10.1021/ja209881f
- ↑ Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Tokatlidis K. An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR. J Am Chem Soc. 2012 Jan 25;134(3):1442-5. Epub 2012 Jan 6. PMID:22224850 doi:10.1021/ja209881f
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