The more we learn, the more diverse it gets: structures, functions and evolution in the Phosphofructokinase Superfamily.

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Tác giả: Jordan A Compton, Wayne M Patrick

Ngôn ngữ: eng

Ký hiệu phân loại: 006.31 Machine learning

Thông tin xuất bản: England : The Biochemical journal , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 744331

The enzyme 6-phosphofructokinase (PFK) phosphorylates d-fructose 6-phosphate, producing d-fructose 1,6-bisphosphate. The canonical version-discovered almost 90 years ago-is ATP-dependent, allosterically regulated and catalyses the first committed step in glycolysis. However, beyond this textbook enzyme, there is fascinating functional and structural variety among PFKs across the tree of life. While PFKs are found in two non-homologous superfamilies, here, we review the universally distributed enzymes in one, the Phosphofructokinase Superfamily. We focus on summarising the diversity within this superfamily. A key partition regards the identity of the phosphate donor, which can be ATP or inorganic pyrophosphate (PPi). Considerable insights into functional and evolutionary aspects of the ATP- and PPi-dependent PFKs have come through structural biology, with 45 structures now available in the Protein Data Bank. One recent highlight was the use of cryoEM and molecular dynamics simulations to illuminate the structural basis of allosteric regulation in human liver PFK. Others were to explore interactions of drug-like small molecules with the PFKs from Trypanosoma brucei and human liver, revealing new routes to antibiotics and immune modulators, respectively. In contrast with the ATP-dependent enzymes, PPi-dependent PFKs are typically non-allosteric and catalyse a readily reversible reaction. Some also play an additional physiological role by phosphorylating d-sedoheptulose 7-phosphate. We discuss why these properties are plausibly ancestral. Finally, we also emphasise how much remains to be discovered. For example, the 45 experimentally determined structures are from only 14 species. Nine decades in, it is still a great time to be studying PFK.
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