3EXG
Crystal structure of the pyruvate dehydrogenase (E1p) component of human pyruvate dehydrogenase complex
Summary for 3EXG
| Entry DOI | 10.2210/pdb3exg/pdb |
| Related | 3EXE 3EXF 3EXH 3EXI |
| Descriptor | Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial, Pyruvate dehydrogenase E1 component subunit beta, mitochondrial, POTASSIUM ION (3 entities in total) |
| Functional Keywords | heterotetramer; thiamine diphosphate-dependent enzyme; disease mutation; glycolysis; leigh syndrome; mitochondrion; oxidoreductase; phosphoprotein; alternative splicing; polymorphism; pyruvate; thiamine pyrophosphate; transit peptide, oxidoreductase |
| Biological source | Homo sapiens (human) More |
| Cellular location | Mitochondrion matrix: P08559 P11177 |
| Total number of polymer chains | 32 |
| Total formula weight | 1256526.88 |
| Authors | Kato, M.,Wynn, R.M.,Chuang, J.L.,Tso, S.-C.,Machius, M.,Li, J.,Chuang, D.T. (deposition date: 2008-10-16, release date: 2008-11-25, Last modification date: 2023-12-27) |
| Primary citation | Kato, M.,Wynn, R.M.,Chuang, J.L.,Tso, S.C.,Machius, M.,Li, J.,Chuang, D.T. Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops. Structure, 16:1849-1859, 2008 Cited by PubMed Abstract: We report the crystal structures of the phosporylated pyruvate dehydrogenase (E1p) component of the human pyruvate dehydrogenase complex (PDC). The complete phosphorylation at Ser264-alpha (site 1) of a variant E1p protein was achieved using robust pyruvate dehydrogenase kinase 4 free of the PDC core. We show that unlike its unmodified counterpart, the presence of a phosphoryl group at Ser264-alpha prevents the cofactor thiamine diphosphate-induced ordering of the two loops carrying the three phosphorylation sites. The disordering of these phosphorylation loops is caused by a previously unrecognized steric clash between the phosphoryl group at site 1 and a nearby Ser266-alpha, which nullifies a hydrogen-bonding network essential for maintaining the loop conformations. The disordered phosphorylation loops impede the binding of lipoyl domains of the PDC core to E1p, negating the reductive acetylation step. This results in the disruption of the substrate channeling in the PDC, leading to the inactivation of this catalytic machine. PubMed: 19081061DOI: 10.1016/j.str.2008.10.010 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.011 Å) |
Structure validation
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