1t9g

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Revision as of 17:15, 12 November 2007

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spinqualitylabelsall models 1t9g, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of the human MCAD:ETF complex

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 AMP and FAD 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

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