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| - | [[Image:1sjd.gif|left|200px]]<br /><applet load="1sjd" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1sjd, resolution 1.87Å" /> | |
| - | '''x-ray structure of o-succinylbenzoate synthase complexed with n-succinyl phenylglycine'''<br /> | |
| | | | |
| - | ==Overview== | + | ==x-ray structure of o-succinylbenzoate synthase complexed with n-succinyl phenylglycine== |
| - | 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. | + | <StructureSection load='1sjd' size='340' side='right'caption='[[1sjd]], [[Resolution|resolution]] 1.87Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1sjd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Amycolatopsis_sp. Amycolatopsis sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SJD FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.87Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NPG:N-SUCCINYL+PHENYLGLYCINE'>NPG</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1sjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sjd OCA], [https://pdbe.org/1sjd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sjd RCSB], [https://www.ebi.ac.uk/pdbsum/1sjd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sjd ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/NSAR_AMYSP NSAR_AMYSP] Acts as a N-succinylamino acid racemase (NSAR) that catalyzes the racemization of N-succinyl-phenylglycine and N-succinyl-methionine (PubMed:14705949, PubMed:24955846). Can catalyze the racemization of a broad range of N-acylamino acids, including N-acetyl-D/L-methionine, N-propionyl-D/L-methionine, N-butyryl-D/L-methionine and N-chloroacetyl-L-valine (PubMed:7766084, PubMed:10194342, PubMed:14705949, PubMed:23130969). Also converts 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) to 2-succinylbenzoate (OSB) (PubMed:10194342, PubMed:14705949, PubMed:24955846). Catalyzes both N-succinylamino acid racemization and OSB synthesis at equivalent rates (PubMed:14705949, PubMed:24955846). NSAR is probably the biological function of this enzyme (Probable).<ref>PMID:10194342</ref> <ref>PMID:14705949</ref> <ref>PMID:23130969</ref> <ref>PMID:24955846</ref> <ref>PMID:7766084</ref> <ref>PMID:16740275</ref> <ref>PMID:24955846</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sj/1sjd_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1sjd ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | 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==
| + | 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<ref>PMID:15134446</ref> |
| - | 1SJD 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 NPG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SJD OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15134446 15134446]
| + | </div> |
| - | [[Category: Amycolatopsis sp.]] | + | <div class="pdbe-citations 1sjd" style="background-color:#fffaf0;"></div> |
| - | [[Category: Single protein]] | + | == References == |
| - | [[Category: Garrett, J.B.]] | + | <references/> |
| - | [[Category: Gerlt, J.A.]] | + | __TOC__ |
| - | [[Category: Holden, H.M.]] | + | </StructureSection> |
| - | [[Category: Rayment, I.]] | + | [[Category: Amycolatopsis sp]] |
| - | [[Category: Taylor-Ringia, E.A.]] | + | [[Category: Large Structures]] |
| - | [[Category: Thoden, J.B.]] | + | [[Category: Garrett JB]] |
| - | [[Category: NPG]]
| + | [[Category: Gerlt JA]] |
| - | [[Category: racemase]]
| + | [[Category: Holden HM]] |
| - | | + | [[Category: Rayment I]] |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 00:37:55 2007''
| + | [[Category: Taylor-Ringia EA]] |
| | + | [[Category: Thoden JB]] |
| Structural highlights
Function
NSAR_AMYSP Acts as a N-succinylamino acid racemase (NSAR) that catalyzes the racemization of N-succinyl-phenylglycine and N-succinyl-methionine (PubMed:14705949, PubMed:24955846). Can catalyze the racemization of a broad range of N-acylamino acids, including N-acetyl-D/L-methionine, N-propionyl-D/L-methionine, N-butyryl-D/L-methionine and N-chloroacetyl-L-valine (PubMed:7766084, PubMed:10194342, PubMed:14705949, PubMed:23130969). Also converts 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) to 2-succinylbenzoate (OSB) (PubMed:10194342, PubMed:14705949, PubMed:24955846). Catalyzes both N-succinylamino acid racemization and OSB synthesis at equivalent rates (PubMed:14705949, PubMed:24955846). NSAR is probably the biological function of this enzyme (Probable).[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Palmer DR, Garrett JB, Sharma V, Meganathan R, Babbitt PC, Gerlt JA. Unexpected divergence of enzyme function and sequence: "N-acylamino acid racemase" is o-succinylbenzoate synthase. Biochemistry. 1999 Apr 6;38(14):4252-8. PMID:10194342 doi:10.1021/bi990140p
- ↑ Taylor Ringia EA, Garrett JB, Thoden JB, Holden HM, Rayment I, Gerlt JA. Evolution of enzymatic activity in the enolase superfamily: functional studies of the promiscuous o-succinylbenzoate synthase from Amycolatopsis. Biochemistry. 2004 Jan 13;43(1):224-9. PMID:14705949 doi:10.1021/bi035815+
- ↑ Baxter S, Royer S, Grogan G, Brown F, Holt-Tiffin KE, Taylor IN, Fotheringham IG, Campopiano DJ. An Improved Racemase/Acylase Biotransformation for the Preparation of Enantiomerically Pure Amino Acids. J Am Chem Soc. 2012 Nov 15. PMID:23130969 doi:http://dx.doi.org/10.1021/ja305438y
- ↑ McMillan AW, Lopez MS, Zhu M, Morse BC, Yeo IC, Amos J, Hull K, Romo D, Glasner ME. Role of an active site loop in the promiscuous activities of Amycolatopsis sp. T-1-60 NSAR/OSBS. Biochemistry. 2014 Jul 15;53(27):4434-44. PMID:24955846 doi:10.1021/bi500573v
- ↑ Tokuyama S, Hatano K. Purification and properties of thermostable N-acylamino acid racemase from Amycolatopsis sp. TS-1-60. Appl Microbiol Biotechnol. 1995 Mar;42(6):853-9. PMID:7766084 doi:10.1007/BF00191181
- ↑ Glasner ME, Fayazmanesh N, Chiang RA, Sakai A, Jacobson MP, Gerlt JA, Babbitt PC. Evolution of structure and function in the o-succinylbenzoate synthase/N-acylamino acid racemase family of the enolase superfamily. J Mol Biol. 2006 Jun 30;360(1):228-50. PMID:16740275 doi:10.1016/j.jmb.2006.04.055
- ↑ McMillan AW, Lopez MS, Zhu M, Morse BC, Yeo IC, Amos J, Hull K, Romo D, Glasner ME. Role of an active site loop in the promiscuous activities of Amycolatopsis sp. T-1-60 NSAR/OSBS. Biochemistry. 2014 Jul 15;53(27):4434-44. PMID:24955846 doi:10.1021/bi500573v
- ↑ Thoden JB, Taylor Ringia EA, Garrett JB, Gerlt JA, Holden HM, Rayment I. Evolution of enzymatic activity in the enolase superfamily: structural studies of the promiscuous o-succinylbenzoate synthase from Amycolatopsis. Biochemistry. 2004 May 18;43(19):5716-27. PMID:15134446 doi:10.1021/bi0497897
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