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| | <StructureSection load='2a1u' size='340' side='right'caption='[[2a1u]], [[Resolution|resolution]] 2.11Å' scene=''> | | <StructureSection load='2a1u' size='340' side='right'caption='[[2a1u]], [[Resolution|resolution]] 2.11Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2a1u]] is a 2 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=2A1U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2A1U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2a1u]] is a 2 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=2A1U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A1U FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <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=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <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">[[1efv|1efv]], [[1t9g|1t9g]], [[2a1t|2a1t]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1efv|1efv]], [[1t9g|1t9g]], [[2a1t|2a1t]]</div></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2a1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a1u OCA], [http://pdbe.org/2a1u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a1u RCSB], [http://www.ebi.ac.uk/pdbsum/2a1u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2a1u 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=2a1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a1u OCA], [https://pdbe.org/2a1u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a1u RCSB], [https://www.ebi.ac.uk/pdbsum/2a1u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a1u ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ETFA_HUMAN ETFA_HUMAN]] Defects in ETFA are the cause of glutaric aciduria type 2A (GA2A) [MIM:[http://omim.org/entry/231680 231680]]; also known as glutaricaciduria IIA. GA2A is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.<ref>PMID:1882842</ref> <ref>PMID:1430199</ref> [[http://www.uniprot.org/uniprot/ETFB_HUMAN ETFB_HUMAN]] Defects in ETFB are the cause of glutaric aciduria type 2B (GA2B) [MIM:[http://omim.org/entry/231680 231680]]. GA2B is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.<ref>PMID:12815589</ref> <ref>PMID:7912128</ref> | + | [[https://www.uniprot.org/uniprot/ETFA_HUMAN ETFA_HUMAN]] Defects in ETFA are the cause of glutaric aciduria type 2A (GA2A) [MIM:[https://omim.org/entry/231680 231680]]; also known as glutaricaciduria IIA. GA2A is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.<ref>PMID:1882842</ref> <ref>PMID:1430199</ref> [[https://www.uniprot.org/uniprot/ETFB_HUMAN ETFB_HUMAN]] Defects in ETFB are the cause of glutaric aciduria type 2B (GA2B) [MIM:[https://omim.org/entry/231680 231680]]. GA2B is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.<ref>PMID:12815589</ref> <ref>PMID:7912128</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ETFA_HUMAN ETFA_HUMAN]] The electron transfer flavoprotein serves as a specific electron acceptor for several dehydrogenases, including five acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase). [[http://www.uniprot.org/uniprot/ETFB_HUMAN ETFB_HUMAN]] The electron transfer flavoprotein serves as a specific electron acceptor for several dehydrogenases, including five acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase). | + | [[https://www.uniprot.org/uniprot/ETFA_HUMAN ETFA_HUMAN]] The electron transfer flavoprotein serves as a specific electron acceptor for several dehydrogenases, including five acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase). [[https://www.uniprot.org/uniprot/ETFB_HUMAN ETFB_HUMAN]] The electron transfer flavoprotein serves as a specific electron acceptor for several dehydrogenases, including five acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Structural highlights
Disease
[ETFA_HUMAN] Defects in ETFA are the cause of glutaric aciduria type 2A (GA2A) [MIM:231680]; also known as glutaricaciduria IIA. GA2A is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.[1] [2] [ETFB_HUMAN] Defects in ETFB are the cause of glutaric aciduria type 2B (GA2B) [MIM:231680]. GA2B is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.[3] [4]
Function
[ETFA_HUMAN] The electron transfer flavoprotein serves as a specific electron acceptor for several dehydrogenases, including five acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase). [ETFB_HUMAN] The electron transfer flavoprotein serves as a specific electron acceptor for several dehydrogenases, including five acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Crystal structures of protein complexes with electron-transferring flavoprotein (ETF) have revealed a dual protein-protein interface with one region serving as anchor while the ETF FAD domain samples available space within the complex. We show that mutation of the conserved Glu-165beta in human ETF leads to drastically modulated rates of interprotein electron transfer with both medium chain acyl-CoA dehydrogenase and dimethylglycine dehydrogenase. The crystal structure of free E165betaA ETF is essentially identical to that of wild-type ETF, but the crystal structure of the E165betaA ETF.medium chain acyl-CoA dehydrogenase complex reveals clear electron density for the FAD domain in a position optimal for fast interprotein electron transfer. Based on our observations, we present a dynamic multistate model for conformational sampling that for the wild-type ETF. medium chain acyl-CoA dehydrogenase complex involves random motion between three distinct positions for the ETF FAD domain. ETF Glu-165beta plays a key role in stabilizing positions incompatible with fast interprotein electron transfer, thus ensuring high rates of complex dissociation.
Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein.,Toogood HS, van Thiel A, Scrutton NS, Leys D J Biol Chem. 2005 Aug 26;280(34):30361-6. Epub 2005 Jun 23. PMID:15975918[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Indo Y, Glassberg R, Yokota I, Tanaka K. Molecular characterization of variant alpha-subunit of electron transfer flavoprotein in three patients with glutaric acidemia type II--and identification of glycine substitution for valine-157 in the sequence of the precursor, producing an unstable mature protein in a patient. Am J Hum Genet. 1991 Sep;49(3):575-80. PMID:1882842
- ↑ Freneaux E, Sheffield VC, Molin L, Shires A, Rhead WJ. Glutaric acidemia type II. Heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha subunit of electron transfer flavoprotein in eight patients. J Clin Invest. 1992 Nov;90(5):1679-86. PMID:1430199 doi:http://dx.doi.org/10.1172/JCI116040
- ↑ Olsen RK, Andresen BS, Christensen E, Bross P, Skovby F, Gregersen N. Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Hum Mutat. 2003 Jul;22(1):12-23. PMID:12815589 doi:10.1002/humu.10226
- ↑ Colombo I, Finocchiaro G, Garavaglia B, Garbuglio N, Yamaguchi S, Frerman FE, Berra B, DiDonato S. Mutations and polymorphisms of the gene encoding the beta-subunit of the electron transfer flavoprotein in three patients with glutaric acidemia type II. Hum Mol Genet. 1994 Mar;3(3):429-35. PMID:7912128
- ↑ Toogood HS, van Thiel A, Scrutton NS, Leys D. Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein. J Biol Chem. 2005 Aug 26;280(34):30361-6. Epub 2005 Jun 23. PMID:15975918 doi:10.1074/jbc.M505562200
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