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PDBsum entry 2wzc
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References listed in PDB file
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Key reference
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Title
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Transition state analogue structures of human phosphoglycerate kinase establish the importance of charge balance in catalysis.
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Authors
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M.J.Cliff,
M.W.Bowler,
A.Varga,
J.P.Marston,
J.Szabó,
A.M.Hounslow,
N.J.Baxter,
G.M.Blackburn,
M.Vas,
J.P.Waltho.
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Ref.
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J Am Chem Soc, 2010,
132,
6507-6516.
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PubMed id
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Abstract
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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)(-).
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