1efv
From Proteopedia
(New page: 200px<br /> <applet load="1efv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1efv, resolution 2.1Å" /> '''THREE-DIMENSIONAL ST...) |
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| - | [[Image:1efv.gif|left|200px]]<br /> | + | [[Image:1efv.gif|left|200px]]<br /><applet load="1efv" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1efv" size=" | + | |
caption="1efv, resolution 2.1Å" /> | caption="1efv, resolution 2.1Å" /> | ||
'''THREE-DIMENSIONAL STRUCTURE OF HUMAN ELECTRON TRANSFER FLAVOPROTEIN TO 2.1 A RESOLUTION'''<br /> | '''THREE-DIMENSIONAL STRUCTURE OF HUMAN ELECTRON TRANSFER FLAVOPROTEIN TO 2.1 A RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mammalian electron transfer flavoproteins (ETF) are heterodimers | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1EFV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FAD and AMP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1EFV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=AMP:'>AMP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EFV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Frerman, F | + | [[Category: Frerman, F E.]] |
| - | [[Category: Kim, J | + | [[Category: Kim, J J.P.]] |
| - | [[Category: Roberts, D | + | [[Category: Roberts, D L.]] |
[[Category: AMP]] | [[Category: AMP]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
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[[Category: glutaric acidemia type ii]] | [[Category: glutaric acidemia type ii]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:27:17 2008'' |
Revision as of 10:27, 21 February 2008
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THREE-DIMENSIONAL STRUCTURE OF HUMAN ELECTRON TRANSFER FLAVOPROTEIN TO 2.1 A RESOLUTION
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Glutaricaciduria, type IIA OMIM:[608053], Glutaricaciduria, type IIB OMIM:[130410]
About this Structure
1EFV is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
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
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