Conformational dynamics in phosphoglycerate kinase, an open and shut case?. Issue 13 (15th May 2013)

• Record Type: Journal Article
• Authors: Bowler, Matthew W.
• Is Part Of: FEBS letters. Volume 587:Issue 13(2013)
• Page Start: 1878
• Page End: 1883
• Publication Date: 2013-05-15
• Subjects: hPGK -- human phosphoglycerate kinase -- 3PG -- 3-phosphoglycerate -- 1, 3BPG -- bisphosphoglycerate -- Enzyme mechanism -- Phosphoryl transfer -- SAXS; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.05.012
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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 ofl ‐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.