2WFA

Structure of Beta-Phosphoglucomutase inhibited with Beryllium trifluoride, in an open conformation.

Summary for 2WFA

• Entry DOI: 10.2210/pdb2wfa/pdb
• Related: 1LVH 1O03 1O08 1Z4N 1Z4O 1ZOL 2WF5 2WF6 2WF7 2WF8 2WF9
• Descriptor: BETA-PHOSPHOGLUCOMUTASE, MAGNESIUM ION, BERYLLIUM TRIFLUORIDE ION, ... (4 entities in total)
• Functional Keywords: isomerase, phosphotransferase, transition state analogue, haloacid dehalogenase superfamily
• Biological source: LACTOCOCCUS LACTIS
• Total number of polymer chains: 1
• Total formula weight: 24329.91

Authors

Bowler, M.W.,Baxter, N.J.,Webster, C.E.,Pollard, S.,Alizadeh, T.,Hounslow, A.M.,Cliff, M.J.,Bermel, W.,Williams, N.H.,Hollfelder, F.,Blackburn, G.M.,Waltho, J.P. (deposition date: 2009-04-03, release date: 2010-05-26, Last modification date: 2024-05-08)

Primary citation

Griffin, J.L.,Bowler, M.W.,Baxter, N.J.,Leigh, K.N.,Dannatt, H.R.,Hounslow, A.M.,Blackburn, G.M.,Webster, C.E.,Cliff, M.J.,Waltho, J.P.
Near Attack Conformers Dominate Beta-Phosphoglucomutase Complexes Where Geometry and Charge Distribution Reflect Those of Substrate.
Proc.Natl.Acad.Sci.USA, 109:6910-, 2012

PubMed Abstract: Experimental observations of fluoromagnesate and fluoroaluminate complexes of β-phosphoglucomutase (β-PGM) have demonstrated the importance of charge balance in transition-state stabilization for phosphoryl transfer enzymes. Here, direct observations of ground-state analog complexes of β-PGM involving trifluoroberyllate establish that when the geometry and charge distribution closely match those of the substrate, the distribution of conformers in solution and in the crystal predominantly places the reacting centers in van der Waals proximity. Importantly, two variants are found, both of which satisfy the criteria for near attack conformers. In one variant, the aspartate general base for the reaction is remote from the nucleophile. The nucleophile remains protonated and forms a nonproductive hydrogen bond to the phosphate surrogate. In the other variant, the general base forms a hydrogen bond to the nucleophile that is now correctly orientated for the chemical transfer step. By contrast, in the absence of substrate, the solvent surrounding the phosphate surrogate is arranged to disfavor nucleophilic attack by water. Taken together, the trifluoroberyllate complexes of β-PGM provide a picture of how the enzyme is able to organize itself for the chemical step in catalysis through the population of intermediates that respond to increasing proximity of the nucleophile. These experimental observations show how the enzyme is capable of stabilizing the reaction pathway toward the transition state and also of minimizing unproductive catalysis of aspartyl phosphate hydrolysis.

PubMed: 22505741
DOI: 10.1073/PNAS.1116855109

Experimental method

X-RAY DIFFRACTION (1.65 Å)