2XE7

The complete reaction cycle of human phosphoglycerate kinase: The open ternary complex with 3PG and ADP

Summary for 2XE7

• Entry DOI: 10.2210/pdb2xe7/pdb
• Related: 2WZB 2WZC 2WZD 2X13 2X14 2X15 2XE6 2XE8
• Descriptor: PHOSPHOGLYCERATE KINASE 1, 3-PHOSPHOGLYCERIC ACID, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: transition state analogue, hereditary hemolytic anemia, phosphoprotein, glycolysis, transferase, phosphoryl transfer, nucleotide-binding, domain motions
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P00558
• Total number of polymer chains: 1
• Total formula weight: 45285.88

Authors

Cliff, M.J.,Baxter, N.J.,Blackburn, G.M.,Merli, A.,Vas, M.,Waltho, J.P.,Bowler, M.W. (deposition date: 2010-05-11, release date: 2011-01-19, Last modification date: 2023-12-20)

Primary citation

Zerrad, L.,Merli, A.,Schroder, G.F.,Varga, A.,Graczer, E.,Pernot, P.,Round, A.,Vas, M.,Bowler, M.W.
A Spring Loaded Release Mechanism Regulates Domain Movement and Catalysis in Phosphoglycerate Kinase.
J.Biol.Chem., 286:14040-, 2011

PubMed 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.

PubMed: 21349853
DOI: 10.1074/JBC.M110.206813

Experimental method

X-RAY DIFFRACTION (2.2 Å)