Conformational dynamics in phosphoglycerate kinase, an open and shut case?

• Published in: FEBS letters Vol. 587; no. 13; pp. 1878 - 1883
• Main Author: Bowler, Matthew W.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 27.06.2013
• Subjects: 1,3BPG; 3-phosphoglycerate; 3PG; adenosine triphosphate; bisphosphoglycerate; carcinogenesis; catalytic activity; Catalytic Domain; crystal structure; Enzyme mechanism; glycolysis; hPGK; human phosphoglycerate kinase; Humans; Models, Molecular; phosphoglycerate kinase; Phosphoglycerate Kinase - chemistry; Phosphoryl transfer; Phosphorylation; Protein Structure, Secondary; Retroviridae; SAXS; Surface Properties; X-ray diffraction; 1,3BPG; 3PG; Enzyme mechanism; hPGK; Phosphoryl transfer; SAXS
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1016/j.febslet.2013.05.012

Domain motions are essential to many catalytic mechanisms in enzymes but they are often difficult to study. X-ray crystal structures can provide molecular details of snapshots of catalysis but many states important in the cycle remain inaccessible using this technique. Phosphoglycerate kinase (PGK) undergoes large domain movements in order to catalyse the production of ATP. PGK is the enzyme responsible for the first ATP generating step of glycolysis and has been implicated in oncogenesis and the in vivo activation of l-nucleoside pro-drugs effective against retroviruses. Its mechanism requires considerable hinge bending to bring the substrates into proximity in order for phosphoryl transfer to occur. The enzyme has been the subject of intense study for decades but new crystal structures, methods in solution scattering and modelling techniques are throwing light on the dynamics of catalysis of this archetypal kinase. Here, I argue that Brownian forces acting on the protein are the dominant factor in the catalytic cycle and that the enzyme has evolved measures to harness this force for efficient catalysis.