2f5z

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Revision as of 19:53, 12 November 2007

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spinqualitylabelsall models 2f5z, resolution 2.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of Human Dihydrolipoamide Dehydrogenase (E3) Complexed to the E3-Binding Domain of Human E3-Binding Protein

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The 9.5 MDa human pyruvate dehydrogenase complex (PDC) utilizes the, specific dihydrolipoamide dehydrogenase (E3) binding protein (E3BP) to, tether the essential E3 component to the 60-meric core of the complex., Here, we report crystal structures of the binding domain (E3BD) of human, E3BP alone and in complex with human E3 at 1.6 angstroms and 2.2, angstroms, respectively. The latter structure shows that residues from, E3BD contact E3 across its 2-fold axis, resulting in one E3BD binding site, on the E3 homodimer. Negligible conformational changes occur in E3BD upon, its high-affinity binding to E3. Modifications of E3BD residues at the, center of the E3BD/E3 interface impede E3 binding far more severely than, those of residues on the periphery, validating the "hot spot" paradigm for, protein interactions. A cluster of disease-causing E3 mutations located, near the center of the E3BD/E3 interface prevents the efficient, recruitment of these E3 variants by E3BP into the PDC, leading to the, dysfunction of the PDC catalytic machine.

Disease

Known diseases associated with this structure: Lacticacidemia due to PDX1 deficiency OMIM:[608769], Leigh syndrome OMIM:[238331], Leukocyte adhesion deficiency OMIM:[600065], Maple syrup urine disease, type III OMIM:[238331]

About this Structure

2F5Z is a Protein complex structure of sequences from Homo sapiens with SO4 and FAD as ligands. Active as Dihydrolipoyl dehydrogenase, with EC number 1.8.1.4 Full crystallographic information is available from OCA.

Reference

Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex., Brautigam CA, Wynn RM, Chuang JL, Machius M, Tomchick DR, Chuang DT, Structure. 2006 Mar;14(3):611-21. Epub 2006 Jan 26. PMID:16442803

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