1efv

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Revision as of 07:20, 20 December 2017

THREE-DIMENSIONAL STRUCTURE OF HUMAN ELECTRON TRANSFER FLAVOPROTEIN TO 2.1 A RESOLUTION

Structural highlights

1efv is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Mammalian electron transfer flavoproteins (ETF) are heterodimers containing a single equivalent of flavin adenine dinucleotide (FAD). They function as electron shuttles between primary flavoprotein dehydrogenases involved in mitochondrial fatty acid and amino acid catabolism and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. The structure of human ETF solved to 2.1-A resolution reveals that the ETF molecule is comprised of three distinct domains: two domains are contributed by the alpha subunit and the third domain is made up entirely by the beta subunit. The N-terminal portion of the alpha subunit and the majority of the beta subunit have identical polypeptide folds, in the absence of any sequence homology. FAD lies in a cleft between the two subunits, with most of the FAD molecule residing in the C-terminal portion of the alpha subunit. Alignment of all the known sequences for the ETF alpha subunits together with the putative FixB gene product shows that the residues directly involved in FAD binding are conserved. A hydrogen bond is formed between the N5 of the FAD isoalloxazine ring and the hydroxyl side chain of alpha T266, suggesting why the pathogenic mutation, alpha T266M, affects ETF activity in patients with glutaric acidemia type II. Hydrogen bonds between the 4'-hydroxyl of the ribityl chain of FAD and N1 of the isoalloxazine ring, and between alpha H286 and the C2-carbonyl oxygen of the isoalloxazine ring, may play a role in the stabilization of the anionic semiquinone. With the known structure of medium chain acyl-CoA dehydrogenase, we hypothesize a possible structure for docking the two proteins.

Three-dimensional structure of human electron transfer flavoprotein to 2.1-A resolution.,Roberts DL, Frerman FE, Kim JJ Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14355-60. PMID:8962055^[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
↑ Roberts DL, Frerman FE, Kim JJ. Three-dimensional structure of human electron transfer flavoprotein to 2.1-A resolution. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14355-60. PMID:8962055

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1efv"

@@ Line 1: / Line 1: @@
 ==THREE-DIMENSIONAL STRUCTURE OF HUMAN ELECTRON TRANSFER FLAVOPROTEIN TO 2.1 A RESOLUTION==
 <StructureSection load='1efv' size='340' side='right' caption='[[1efv]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[1efv]] 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=1EFV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EFV FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></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=1efv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1efv OCA], [http://pdbe.org/1efv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1efv RCSB], [http://www.ebi.ac.uk/pdbsum/1efv PDBsum]</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=1efv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1efv OCA], [http://pdbe.org/1efv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1efv RCSB], [http://www.ebi.ac.uk/pdbsum/1efv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1efv ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ef/1efv_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ef/1efv_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1efv

From Proteopedia

Revision as of 07:20, 20 December 2017

THREE-DIMENSIONAL STRUCTURE OF HUMAN ELECTRON TRANSFER FLAVOPROTEIN TO 2.1 A RESOLUTION

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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