1t9g
From Proteopedia
(Difference between revisions)
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- | + | ==Structure of the human MCAD:ETF complex== | |
- | === | + | <StructureSection load='1t9g' size='340' side='right' caption='[[1t9g]], [[Resolution|resolution]] 2.90Å' scene=''> |
- | + | == Structural highlights == | |
+ | <table><tr><td colspan='2'>[[1t9g]] is a 6 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=1T9G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T9G FirstGlance]. <br> | ||
+ | </td></tr><tr><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><br> | ||
+ | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1udy|1udy]], [[1efv|1efv]], [[1o94|1o94]]</td></tr> | ||
+ | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACADM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), ETFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), ETFB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
+ | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acyl-CoA_dehydrogenase Acyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.3 1.3.99.3] </span></td></tr> | ||
+ | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t9g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t9g RCSB], [http://www.ebi.ac.uk/pdbsum/1t9g PDBsum]</span></td></tr> | ||
+ | <table> | ||
+ | == Disease == | ||
+ | [[http://www.uniprot.org/uniprot/ACADM_HUMAN ACADM_HUMAN]] Defects in ACADM are the cause of acyl-CoA dehydrogenase medium-chain deficiency (ACADMD) [MIM:[http://omim.org/entry/201450 201450]]. It is an autosomal recessive disease which causes fasting hypoglycemia, hepatic dysfunction, and encephalopathy, often resulting in death in infancy.<ref>PMID:2393404</ref> <ref>PMID:2394825</ref> <ref>PMID:2251268</ref> <ref>PMID:1684086</ref> <ref>PMID:1902818</ref> <ref>PMID:1671131</ref> <ref>PMID:8198141</ref> <ref>PMID:7603790</ref> <ref>PMID:7929823</ref> <ref>PMID:9158144</ref> <ref>PMID:9882619</ref> <ref>PMID:10767181</ref> <ref>PMID:11349232</ref> <ref>PMID:11409868</ref> <ref>PMID:11486912</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> [[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> | ||
+ | == Function == | ||
+ | [[http://www.uniprot.org/uniprot/ACADM_HUMAN ACADM_HUMAN]] This enzyme is specific for acyl chain lengths of 4 to 16. [[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). [[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). | ||
+ | == Evolutionary Conservation == | ||
+ | [[Image:Consurf_key_small.gif|200px|right]] | ||
+ | Check<jmol> | ||
+ | <jmolCheckbox> | ||
+ | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t9/1t9g_consurf.spt"</scriptWhenChecked> | ||
+ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
+ | <text>to colour the structure by Evolutionary Conservation</text> | ||
+ | </jmolCheckbox> | ||
+ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
+ | <div style="clear:both"></div> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | The crystal structure of the human electron transferring flavoprotein (ETF).medium chain acyl-CoA dehydrogenase (MCAD) complex reveals a dual mode of protein-protein interaction, imparting both specificity and promiscuity in the interaction of ETF with a range of structurally distinct primary dehydrogenases. ETF partitions the functions of partner binding and electron transfer between (i) the recognition loop, which acts as a static anchor at the ETF.MCAD interface, and (ii) the highly mobile redox active FAD domain. Together, these enable the FAD domain of ETF to sample a range of conformations, some compatible with fast interprotein electron transfer. Disorders in amino acid or fatty acid catabolism can be attributed to mutations at the protein-protein interface. Crucially, complex formation triggers mobility of the FAD domain, an induced disorder that contrasts with general models of protein-protein interaction by induced fit mechanisms. The subsequent interfacial motion in the MCAD.ETF complex is the basis for the interaction of ETF with structurally diverse protein partners. Solution studies using ETF and MCAD with mutations at the protein-protein interface support this dynamic model and indicate ionic interactions between MCAD Glu(212) and ETF Arg alpha(249) are likely to transiently stabilize productive conformations of the FAD domain leading to enhanced electron transfer rates between both partners. | ||
- | + | Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex.,Toogood HS, van Thiel A, Basran J, Sutcliffe MJ, Scrutton NS, Leys D J Biol Chem. 2004 Jul 30;279(31):32904-12. Epub 2004 May 24. PMID:15159392<ref>PMID:15159392</ref> | |
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- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Acyl-CoA dehydrogenase|Acyl-CoA dehydrogenase]] | *[[Acyl-CoA dehydrogenase|Acyl-CoA dehydrogenase]] | ||
- | + | == References == | |
- | == | + | <references/> |
- | + | __TOC__ | |
+ | </StructureSection> | ||
[[Category: Acyl-CoA dehydrogenase]] | [[Category: Acyl-CoA dehydrogenase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] |
Revision as of 21:58, 29 September 2014
Structure of the human MCAD:ETF complex
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Categories: Acyl-CoA dehydrogenase | Homo sapiens | Basran, J. | Leys, D. | Scrutton, N S. | Sutcliffe, M J. | Thiel, A van. | Toogood, H S. | Electron transfer | Electron transport | Fatty acid oxidation | Human electron transferring flavoprotein | Human medium chain acyl coa dehydrogenase | Oxidoreductase | Protein:protein complex