2WZC

The catalytically active fully closed conformation of human phosphoglycerate kinase in complex with ADP, 3PG and aluminium tetrafluoride

Summary for 2WZC

• Entry DOI: 10.2210/pdb2wzc/pdb
• Related: 2WZB 2WZD
• Descriptor: PHOSPHOGLYCERATE KINASE 1, MAGNESIUM ION, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: hereditary hemolytic anemia, transferase, phosphoprotein, kinase, glycolysis, nucleotide-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P00558
• Total number of polymer chains: 1
• Total formula weight: 45317.42

Authors

Bowler, M.W.,Cliff, M.J.,Marston, J.P.M.,Baxter, N.J.,Hownslow, A.M.H.,Varga, A.V.,Szabo, J.,Vas, M.,Blackburn, G.M.,Waltho, J.P. (deposition date: 2009-11-27, release date: 2010-04-14, Last modification date: 2023-12-20)

Primary citation

Cliff, M.J.,Bowler, M.W.,Szabo, J.,Marston, J.P.M.,Varga, A.V.,Hownslow, A.M.H.,Baxter, N.J.,Blackburn, G.M.,Vas, M.,Waltho, J.P.
Transition State Analogue Structures of Human Phosphoglycerate Kinase Establish the Importance of Charge Balance in Catalysis.
J.Am.Chem.Soc., 132:6507-, 2010

PubMed Abstract: Transition state analogue (TSA) complexes formed by phosphoglycerate kinase (PGK) have been used to test the hypothesis that balancing of charge within the transition state dominates enzyme-catalyzed phosphoryl transfer. High-resolution structures of trifluoromagnesate (MgF(3)(-)) and tetrafluoroaluminate (AlF(4)(-)) complexes of PGK have been determined using X-ray crystallography and (19)F-based NMR methods, revealing the nature of the catalytically relevant state of this archetypal metabolic kinase. Importantly, the side chain of K219, which coordinates the alpha-phosphate group in previous ground state structures, is sequestered into coordinating the metal fluoride, thereby creating a charge environment complementary to the transferring phosphoryl group. In line with the dominance of charge balance in transition state organization, the substitution K219A induces a corresponding reduction in charge in the bound aluminum fluoride species, which changes to a trifluoroaluminate (AlF(3)(0)) complex. The AlF(3)(0) moiety retains the octahedral geometry observed within AlF(4)(-) TSA complexes, which endorses the proposal that some of the widely reported trigonal AlF(3)(0) complexes of phosphoryl transfer enzymes may have been misassigned and in reality contain MgF(3)(-).

PubMed: 20397725
DOI: 10.1021/JA100974T

Experimental method

X-RAY DIFFRACTION (1.5 Å)