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PDBsum entry 1sjb
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Lyase, isomerase
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PDB id
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1sjb
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Evolution of enzymatic activity in the enolase superfamily: structural studies of the promiscuous o-Succinylbenzoate synthase from amycolatopsis.
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Authors
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J.B.Thoden,
E.A.Taylor ringia,
J.B.Garrett,
J.A.Gerlt,
H.M.Holden,
I.Rayment.
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Ref.
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Biochemistry, 2004,
43,
5716-5727.
[DOI no: ]
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PubMed id
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Abstract
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Divergent evolution of enzyme function is commonly explained by a gene
duplication event followed by mutational changes that allow the protein encoded
by the copy to acquire a new function. An alternate hypothesis is that this
process is facilitated when the progenitor enzyme acquires a second function
while maintaining the original activity. This phenomenon has been suggested to
occur in the o-succinylbenzoate synthase (OSBS) from a species of Amycolatopsis
that catalyzes not only the physiological syn-dehydration reaction of
2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate but also an accidental
racemization of N-acylamino acids [Palmer, D. R., Garrett, J. B., Sharma, V.,
Meganathan, R., Babbitt, P. C., and Gerlt, J. A. (1999) Biochemistry 38,
4252-4258]. To understand the molecular basis of this promiscuity,
three-dimensional structures of liganded complexes of this enzyme have been
determined, including the product of the OSBS reaction and three N-acylamino
acid substrates for the N-acylamino acid racemase (NAAAR) reaction,
N-acetylmethionine, N-succinylmethionine, and N-succinylphenylglycine, to 2.2,
2.3, 2.1, and 1.9 A resolution, respectively. These structures show how the
active-site cavity can accommodate both the hydrophobic substrate for the OSBS
reaction and the substrates for the accidental NAAAR reaction. As expected, the
N-acylamino acid is sandwiched between lysines 163 and 263, which function as
the catalytic bases for the abstraction of the alpha-proton in the (R)- and
(S)-racemization reactions, respectively [Taylor Ringia, E. A., Garrett, J. B,
Thoden, J. B., Holden, H. M., Rayment, I., and Gerlt, J. A. (2004) Biochemistry
42, 224-229]. Importantly, the protein forms specific favorable interactions
with the hydrophobic amino acid side chain, alpha-carbon, carboxylate, and the
polar components of the N-acyl linkage. Accommodation of the components of the
N-acyl linkage appears to be the reason that this enzyme is capable of a
racemization reaction on these substrates, whereas the orthologous OSBS from
Escherichia coli lacks this functionality.
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