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Role of Flexible Linkers

Role of Flexible Linkers. Pieter Jasperse and Dlawer Ala’Aldeen British University Hospital Nottingham UK. International Collaboration. Dlawer Ala’Aldeen (Nottingham) is a vaccine expert and identified the genes of the pyruvate dehydrogenase complex from an outer membrane preparation

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Role of Flexible Linkers

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  1. Role of Flexible Linkers Pieter Jasperse and Dlawer Ala’Aldeen British University Hospital Nottingham UK

  2. International Collaboration • Dlawer Ala’Aldeen (Nottingham) is a vaccine expert and identified the genes of the pyruvate dehydrogenase complex from an outer membrane preparation • The group of Aart de Kok (Wageningen) has experience with the flexible lipoyl domain

  3. Pyruvate Dehydrogenase Complex

  4. S S =O aa 0 400 500 600 100 200 300 HN E3 K43 FAD NAD central interface lipoyl Domain Structure E3 E3 component from Pyruvate Dehydrogenase Complex (PDHC): Lipoamide dehydrogenase (E3) from Neisseria meningitidis

  5. Objectives • Catalysis of enzyme requires high flexibility of domains of the complex which carry the substrate • Study flexibility by NMR using 15N-enriched material

  6. Results • 2D and 3D NMR reveals 35 sharp resonances which could be assigned to the linker residues • The linker has an extended conformation • The tc of all linker residues falls in the range of 7-12 ns • The mobility of lipoyl domain is restricted in intact protein

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