Journal Article

PreJuSER-16685

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Spring Loaded Release Mechanism Regulates Domain Movement and Catalysis in Phosphoglycerate Kinase.

Zerrad, L.FZJ* ; Merli, A.FZJ* ; Schröder, G. F.FZJ* ; Varga, A.FZJ* ; Gráczer, E.FZJ* ; Pernot, P.FZJ* ; Round, A.FZJ* ; Vas, M.FZJ* ; Bowler, M. W.FZJ*

2011
Soc. Bethesda, Md.

This record in other databases:      

Please use a persistent id in citations: doi:10.1074/jbc.M110.206813

Abstract: Phosphoglycerate kinase (PGK) is the enzyme responsible for the first ATP-generating step of glycolysis and has been implicated extensively in oncogenesis and its development. Solution small angle x-ray scattering (SAXS) data, in combination with crystal structures of the enzyme in complex with substrate and product analogues, reveal a new conformation for the resting state of the enzyme and demonstrate the role of substrate binding in the preparation of the enzyme for domain closure. Comparison of the x-ray scattering curves of the enzyme in different states with crystal structures has allowed the complete reaction cycle to be resolved both structurally and temporally. The enzyme appears to spend most of its time in a fully open conformation with short periods of closure and catalysis, thereby allowing the rapid diffusion of substrates and products in and out of the binding sites. Analysis of the open apoenzyme structure, defined through deformable elastic network refinement against the SAXS data, suggests that interactions in a mostly buried hydrophobic region may favor the open conformation. This patch is exposed on domain closure, making the open conformation more thermodynamically stable. Ionic interactions act to maintain the closed conformation to allow catalysis. The short time PGK spends in the closed conformation and its strong tendency to rest in an open conformation imply a spring-loaded release mechanism to regulate domain movement, catalysis, and efficient product release.

Keyword(s): Adenosine Triphosphate: chemistry (MeSH) ; Amino Acid Sequence (MeSH) ; Animals (MeSH) ; Binding Sites (MeSH) ; Biophysics: methods (MeSH) ; Catalysis (MeSH) ; Crystallography, X-Ray: methods (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Molecular Sequence Data (MeSH) ; Phosphoglycerate Kinase: chemistry (MeSH) ; Protein Conformation (MeSH) ; Protein Structure, Secondary (MeSH) ; Protein Structure, Tertiary (MeSH) ; Scattering, Radiation (MeSH) ; Sequence Homology, Amino Acid (MeSH) ; Thermodynamics (MeSH) ; Adenosine Triphosphate ; Phosphoglycerate Kinase ; J

Note: This work was supported in part by Hungarian National Research Grant 77978.

---

Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (P33)
2. BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung (P45)

Appears in the scientific report 2011

---