Pyruvate phosphate dikinase: Difference between revisions

PPDK assembles into homodimers of ~95 kD subunit molecular mass. The monomer is comprised of three domains and contains two distinct reaction centers located ~45 Å apart; the PEP/pyruvate partial reaction (step 1) takes place at the C-terminal domain (adopting an α/β barrel fold) and the nucleotide and inorganic phosphate partial reactions (steps 2 and 3) take place at the N-terminal domain (adopting the ATP grasp fold with two sub domains). A central domain, tethered to the N- and C-terminal domains by two closely-associated linkers, contains a phosphorylatable histidine residue (His455). To shuttle the phosphoryl group between the two reaction centers, the His-domain undergoes a ~110° swivel motion around the two linkers. In addition, upon detachment from the His-domain, the two nucleotide-binding sub domains undergo a ~40° hinge motion that opens the active site cleft.

''The movie depicts the catalytic reaction involving three in-line phosphotransfers and the accompanied protein conformational transitions. This is a model based on crystal structures of PPDK from '''Clostridium symbiosum''' in the two extreme conformational states shown to the left and of complexes bound to substrate analogs, phosphonopyruvate and 5'-adenylyl-β,γ-imidodiphosphate (AMPPNP). The nucleotide binding subdomains are colored green and blue. The PEP binding domain is colored cyan. The His-domain is colored yellow, and the linker segments that connect the His-domain to the partner domains are colored red. Ligands and the catalytic histidine are depicted in stick models with the atomic color scheme: Carbon – gray, Nitrogen – blue, Oxygen – red, Phosphorous – green, Magnesium – magenta. Note that the reaction pregresses in the movie in the reverse direction; steps 3 and 2 occur first followed by step 1. The movie was created by Kap Lim and osnat Herzberg''<br>