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PDBsum entry 3b3s
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References listed in PDB file
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Key reference
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Title
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Zinc coordination geometry and ligand binding affinity: the structural and kinetic analysis of the second-Shell serine 228 residue and the methionine 180 residue of the aminopeptidase from vibrio proteolyticus.
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Authors
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N.J.Ataie,
Q.Q.Hoang,
M.P.Zahniser,
Y.Tu,
A.Milne,
G.A.Petsko,
D.Ringe.
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Ref.
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Biochemistry, 2008,
47,
7673-7683.
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PubMed id
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Abstract
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The chemical properties of zinc make it an ideal metal to study the role of
coordination strain in enzymatic rate enhancement. The zinc ion and the protein
residues that are bound directly to the zinc ion represent a functional
charge/dipole complex, and polarization of this complex, which translates to
coordination distortion, may tune electrophilicity, and hence, reactivity.
Conserved protein residues outside of the charge/dipole complex, such as
second-shell residues, may play a role in supporting the electronic strain
produced as a consequence of functional polarization. To test the correlation
between charge/dipole polarity and ligand binding affinity, structure-function
studies were carried out on the dizinc aminopeptidase from Vibrio proteolyticus.
Alanine substitutions of S228 and M180 resulted in catalytically diminished
enzymes whose crystal structures show very little change in the positions of the
metal ions and the protein residues. However, more detailed inspections of the
crystal structures show small positional changes that account for differences in
the zinc ion coordination geometry. Measurements of the binding affinity of
leucine phosphonic acid, a transition state analogue, and leucine, a product,
show a correlation between coordination geometry and ligand binding affinity.
These results suggest that the coordination number and polarity may tune the
electrophilicity of zinc. This may have provided the evolving enzyme with the
ability to discriminate between reaction coordinate species.
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