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PDBsum entry 1cps
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HydrolasE(C-terminal peptidase)
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PDB id
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1cps
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References listed in PDB file
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Key reference
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Title
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Structural comparison of sulfodiimine and sulfonamide inhibitors in their complexes with zinc enzymes.
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Authors
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A.M.Cappalonga,
R.S.Alexander,
D.W.Christianson.
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Ref.
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J Biol Chem, 1992,
267,
19192-19197.
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PubMed id
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Abstract
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The three-dimensional structure of (L(-)-2-carboxy-3-phenylpropyl)
methylsulfodiimine in its complex with the zinc metalloenzyme carboxypeptidase A
has been determined at 2.25-A resolution by x-ray crystallographic methods. This
is the first example of a sulfodiimine-containing inhibitor binding to a zinc
enzyme, and the structure of the enzyme-inhibitor complex reveals that the
tetrahedral sulfodiimine group coordinates to the active site zinc ion in
unidentate fashion. The zinc-coordinated nitrogen atom of the sulfodiimine group
is also within hydrogen bonding distance to active site base Glu-270;
presumably, the sulfodiimine is ionized and accepts a hydrogen bond from
protonated Glu-270. The other sulfodiimine nitrogen accepts a hydrogen bond from
Arg-127, and the inhibitor binds as a possible analogue of the tetrahedral
transition state (or intermediate) in a promoted water pathway for peptide
hydrolysis. The unidentate sulfodiimine-zinc binding mode observed in this
enzyme-inhibitor complex is reminiscent of that observed in sulfonamide
complexes with the zinc metalloenzyme carbonic anhydrase II, and the structural
features of sulfodiimine- and sulfonamide-zinc interactions exhibit important
similarities among recently determined structures of enzyme-inhibitor complexes:
ionized nitrogens bind to zinc in each structure, and these nitrogens are
engaged in hydrogen bond interactions with neighboring enzyme residues.
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