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PDBsum entry 3bpb
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References listed in PDB file
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Key reference
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Title
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Promiscuous partitioning of a covalent intermediate common in the pentein superfamily.
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Authors
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T.W.Linsky,
A.F.Monzingo,
E.M.Stone,
J.D.Robertus,
W.Fast.
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Ref.
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Chem Biol, 2008,
15,
467-475.
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PubMed id
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Abstract
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Many enzymes in the pentein superfamily use a transient covalent intermediate in
their catalytic mechanisms. Here we trap and determine the structure of a stable
covalent adduct that mimics this intermediate using a mutant dimethylarginine
dimethylaminohydrolase and an alternative substrate. The interactions observed
between the enzyme and trapped adduct suggest an altered angle of attack between
the nucleophiles of the first and second half-reactions of normal catalysis. The
stable covalent adduct is also capable of further reaction. Addition of
imidazole rescues the original hydrolytic activity. Notably, addition of other
amines instead yields substituted arginine products, which arise from
partitioning of the intermediate into the evolutionarily related
amidinotransferase reaction pathway. The enzyme provides both selectivity and
catalysis for the amidinotransferase reaction, underscoring commonalities among
the reaction pathways in this mechanistically diverse enzyme superfamily. The
promiscuous partitioning of this intermediate may also help to illuminate the
evolutionary history of these enzymes.
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