1sjb
From Proteopedia
(New page: 200px<br /><applet load="1sjb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sjb, resolution 2.20Å" /> '''X-ray structure of o...) |
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| - | [[Image:1sjb.gif|left|200px]]<br /><applet load="1sjb" size=" | + | [[Image:1sjb.gif|left|200px]]<br /><applet load="1sjb" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1sjb, resolution 2.20Å" /> | caption="1sjb, resolution 2.20Å" /> | ||
'''X-ray structure of o-succinylbenzoate synthase complexed with o-succinylbenzoic acid'''<br /> | '''X-ray structure of o-succinylbenzoate synthase complexed with o-succinylbenzoic acid'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Divergent evolution of enzyme function is commonly explained by a gene | + | 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== | ==About this Structure== | ||
| - | 1SJB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Amycolatopsis_sp. Amycolatopsis sp.] with MG and OSB as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1SJB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Amycolatopsis_sp. Amycolatopsis sp.] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=OSB:'>OSB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SJB OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Amycolatopsis sp.]] | [[Category: Amycolatopsis sp.]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Garrett, J | + | [[Category: Garrett, J B.]] |
| - | [[Category: Gerlt, J | + | [[Category: Gerlt, J A.]] |
| - | [[Category: Holden, H | + | [[Category: Holden, H M.]] |
[[Category: Rayment, I.]] | [[Category: Rayment, I.]] | ||
| - | [[Category: Taylor-Ringia, E | + | [[Category: Taylor-Ringia, E A.]] |
| - | [[Category: Thoden, J | + | [[Category: Thoden, J B.]] |
[[Category: MG]] | [[Category: MG]] | ||
[[Category: OSB]] | [[Category: OSB]] | ||
[[Category: racemase]] | [[Category: racemase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:02:05 2008'' |
Revision as of 13:02, 21 February 2008
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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 and 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
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