EC Number   |
|---|
   1.2.1.104 | - |
| 1.2.1.104 | asymmetric reconstruction of the active, native pyruvate dehydrogenase complex by cryo-EM as a dynamic assembly. Enzyme clusters form a transient catalytic nanocompartment. The flexible parts of the dehydrogenase factory are notably restricted by a density cloud surrounding single E1p and E3 subunits. This density cloud presumably is composed of E1p and E3. The E1p and E3 proteins are not observed to interact directly with the E2p core but are spatially confined in relative proximity |
| 1.2.1.104 | by cryo-electron microscopy, protein X is found interior to the PDC core as opposed to substituting E2 core subunits as in mammals. Steric occlusion limits protein X binding, resulting in predominantly tetrahedral symmetry |
| 1.2.1.104 | coarse-grained models of E2/E3BP, the two subunits of the massive pyruvate dehydrogenase complex core. Both subunit models show very good structural stability and consistency with those from the atomistic level. The homotrimers and heterotrimers were modeled, and the full WT 60-meric core of the pyruvate dehydrogenase complex is built up. Exploration of the stability of two substitutional models: 40E2+20E3BP and 48E2+12E3BP shows a higher stability and sphericity for the second model. Simulation of C-terminal truncated E2/E3BP cores of different lengths shows the instability of the core assembly and symmetry due to subunit separations |
| 1.2.1.104 | component E1 without cofactors thiamine diphosphate and Mg2+, at 2.32 A resolution. Water molecules may form a hydrogen-bonded linkage between residues Glu571 and Val192, which normally make conserved interactions with the thiamine diphosphate cofactor. A histidine side chain that normally forms hydrogen bonds to thiamine diphosphate is disordered in its absence and partially occupies two sites. No disorder/order loop transformations are evident in the apo-E1 component relative to the holo-E1 enzyme |
| 1.2.1.104 | electron cryotomography, shows that the E1 and E3 subunits of the complex are flexibly tethered about 11 nm away from the E2 core |
| 1.2.1.104 | full and dynamic structural model of full human pyruvate dehydrogenase complex, including binding of the linking arms to the surrounding E1 (pyruvate decarboxylase) and E3 (dihydrolipoamide dehydrogenase) enzymes via their binding domains with variable stoichiometries. An optimal setting of approximately 30 copies of E1 ensures stability of the surrounding E1 and E3 clouds. Decreasing the number of E1s increases the flexibility of the now nonoccupied arms. Their flexibility depends on the presence of other E1s and E3s in the vicinity, even if they are associated with other arms. As one consequence, the radius of gyration decreases with decreasing number of E1s |
| 1.2.1.104 | homology modeling and docking of inhibitor N-((1-((4-amino-2-methylpyrimidin-5-yl)methyl)-5-iodo-1H-1,2,3-triazol-4-yl)methyl)-4-nitrobenzenesulfonamide. The compound can inhibit PDH subunit E1 by occupying the thiamin diphosphate-binding pocket and then blocking PDH E1 bound to thiamin diphosphate as competitive inhibitor |
| 1.2.1.104 | molecular docking of inhibitors and crystallization in complex with inhibitor 3-([1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4,5-dihydro-1H-1,2,3-triazol-4-yl]methyl)-6-bromoquinazolin-4(3H)-one |
| 1.2.1.104 | molecular docking of inhibitors. The acylhydrazone and N-phenylbenzamide moieties can form stronger interactions by hydrogen bonds at the active site of the Escherichia coli pyruvated dehydrogenase complex E1 component compared with that of porcine E1 |
