3u2m

From Proteopedia

(Difference between revisions)

Revision as of 05:55, 13 July 2022

Crystal structure of human ALR mutant C142/145S

Structural highlights

3u2m is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3o55, 3u2l
Gene:	GFER, ALR, HERV1, HPO (HUMAN)
Activity:	Thiol oxidase, with EC number 1.8.3.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3u2m"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human ALR mutant C142/145S==
-<StructureSection load='3u2m' size='340' side='right' caption='[[3u2m]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='3u2m' size='340' side='right'caption='[[3u2m]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3u2m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U2M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3u2m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
+</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>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3o55|3o55]], [[3u2l|3u2l]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3o55|3o55]], [[3u2l|3u2l]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GFER, ALR, HERV1, HPO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GFER, ALR, HERV1, HPO ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thiol_oxidase Thiol oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.3.2 1.8.3.2] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thiol_oxidase Thiol oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.3.2 1.8.3.2] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3u2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u2m OCA], [http://pdbe.org/3u2m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3u2m RCSB], [http://www.ebi.ac.uk/pdbsum/3u2m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3u2m ProSAT]</span></td></tr>
+<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 ==
-[[http://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.
+[[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 ==
-[[http://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>
+[[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 ==
@@ Line 23: / Line 23: @@
 </div>
 <div class="pdbe-citations 3u2m" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Sulfhydryl oxidase 3D structures|Sulfhydryl oxidase 3D structures]]
 == References ==
 <references/>
@@ Line 28: / Line 31: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Thiol oxidase]]
 [[Category: Banci, L]]

3u2m

From Proteopedia

Revision as of 05:55, 13 July 2022

Crystal structure of human ALR mutant C142/145S

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

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