1sjb
From Proteopedia
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X-ray structure of o-succinylbenzoate synthase complexed with o-succinylbenzoic acid
Overview
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.
About this Structure
1SJB is a Single protein structure of sequence from Amycolatopsis sp. with MG and OSB as ligands. Full crystallographic information is available from OCA.
Reference
Evolution of enzymatic activity in the enolase superfamily: structural studies of the promiscuous o-succinylbenzoate synthase from Amycolatopsis., Thoden JB, Taylor Ringia EA, Garrett JB, Gerlt JA, Holden HM, Rayment I, Biochemistry. 2004 May 18;43(19):5716-27. PMID:15134446
Page seeded by OCA on Sun Nov 25 00:37:19 2007
