1t9g
From Proteopedia
(New page: 200px<br /> <applet load="1t9g" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t9g, resolution 2.90Å" /> '''Structure of the hu...) |
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| - | [[Image:1t9g.gif|left|200px]]<br /> | + | [[Image:1t9g.gif|left|200px]]<br /><applet load="1t9g" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1t9g" size=" | + | |
caption="1t9g, resolution 2.90Å" /> | caption="1t9g, resolution 2.90Å" /> | ||
'''Structure of the human MCAD:ETF complex'''<br /> | '''Structure of the human MCAD:ETF complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of the human electron transferring flavoprotein | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1T9G 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 AMP and FAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1T9G 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=AMP:'>AMP</scene> and <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T9G OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Basran, J.]] | [[Category: Basran, J.]] | ||
[[Category: Leys, D.]] | [[Category: Leys, D.]] | ||
| - | [[Category: Scrutton, N | + | [[Category: Scrutton, N S.]] |
| - | [[Category: Sutcliffe, M | + | [[Category: Sutcliffe, M J.]] |
| - | [[Category: Thiel, A | + | [[Category: Thiel, A van.]] |
| - | [[Category: Toogood, H | + | [[Category: Toogood, H S.]] |
[[Category: AMP]] | [[Category: AMP]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
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[[Category: protein:protein complex]] | [[Category: protein:protein complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:11:18 2008'' |
Revision as of 13:11, 21 February 2008
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Structure of the human MCAD:ETF complex
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Acyl-CoA dehydrogenase, medium chain, deficiency of OMIM:[607008], Glutaricaciduria, type IIA OMIM:[608053], Glutaricaciduria, type IIB OMIM:[130410]
About this Structure
1T9G is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Acyl-CoA dehydrogenase, with EC number 1.3.99.3 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 15:11:18 2008
Categories: Acyl-CoA dehydrogenase | Homo sapiens | Protein complex | Basran, J. | Leys, D. | Scrutton, N S. | Sutcliffe, M J. | Thiel, A van. | Toogood, H S. | AMP | FAD | Electron transfer | Fatty acid oxidation | Human electron transferring flavoprotein | Human medium chain acyl coa dehydrogenase | Protein:protein complex
