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| | <StructureSection load='2iht' size='340' side='right'caption='[[2iht]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='2iht' size='340' side='right'caption='[[2iht]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2iht]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/As_4.1611 As 4.1611]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IHT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2iht]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IHT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ceas2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1901 AS 4.1611])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/N(2)-(2-carboxyethyl)arginine_synthase N(2)-(2-carboxyethyl)arginine synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.66 2.5.1.66] </span></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=2iht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iht OCA], [https://pdbe.org/2iht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2iht RCSB], [https://www.ebi.ac.uk/pdbsum/2iht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2iht ProSAT]</span></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=2iht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iht OCA], [https://pdbe.org/2iht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2iht RCSB], [https://www.ebi.ac.uk/pdbsum/2iht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2iht ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CEAS_STRCL CEAS_STRCL] Involved in the biosynthesis of the beta-lactamase inhibitor, clavulanic acid. Catalyzes the thiamine diphosphate (ThDP) dependent condensation of D-glyceraldehyde-3-phosphate (D-G3P) with L-arginine to yield the beta-amino acid, N2-(2-carboxyethyl)arginine (CEA) via a beta-elimination resulting in the formation of an enol which undergoes a second elimination to generate the alpha,beta-unsaturated acryloyl-ThDP.<ref>PMID:18052280</ref> <ref>PMID:19477162</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: As 4 1611]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Caines, M E]] | + | [[Category: Streptomyces clavuligerus]] |
| - | [[Category: Schofield, C J]] | + | [[Category: Caines ME]] |
| - | [[Category: Thiamin diphosphate complex]] | + | [[Category: Schofield CJ]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
2iht is a 4 chain structure with sequence from Streptomyces clavuligerus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CEAS_STRCL Involved in the biosynthesis of the beta-lactamase inhibitor, clavulanic acid. Catalyzes the thiamine diphosphate (ThDP) dependent condensation of D-glyceraldehyde-3-phosphate (D-G3P) with L-arginine to yield the beta-amino acid, N2-(2-carboxyethyl)arginine (CEA) via a beta-elimination resulting in the formation of an enol which undergoes a second elimination to generate the alpha,beta-unsaturated acryloyl-ThDP.[1] [2]
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
N(2)-(2-Carboxyethyl)arginine synthase (CEAS), an unusual thiamin diphosphate (ThDP)-dependent enzyme, catalyses the committed step in the biosynthesis of the b-lactamase inhibitor clavulanic acid in Streptomyces clavuligerus. Crystal structures of tetrameric CEAS-ThDP in complex with the substrate analogues 5-guanidinovaleric acid (GVA) and tartrate, and a structure reflecting a possible enol(ate)-ThDP reaction intermediate are described. The structures suggest overlapping binding sites for the substrates D-glyceraldehyde-3-phosphate (D-G3P) and L-arginine, and are consistent with the proposed CEAS mechanism in which D-G3P binds at the active site and reacts to form an alpha,beta-unsaturated intermediate,which subsequently undergoes (1,4)-Michael addition with the alpha-amino group of L-arginine. Additional solution studies are presented which probe the amino acid substrate tolerance of CEAS, providing further insight into the L-arginine binding site. These findings may facilitate the engineering of CEAS towards the synthesis of alternative beta-amino acid products.
Structural and mechanistic studies on N(2)-(2-carboxyethyl)arginine synthase.,Caines ME, Sorensen JL, Schofield CJ Biochem Biophys Res Commun. 2009 Aug 7;385(4):512-7. Epub 2009 May 27. PMID:19477162[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Merski M, Townsend CA. Observation of an acryloyl-thiamin diphosphate adduct in the first step of clavulanic acid biosynthesis. J Am Chem Soc. 2007 Dec 26;129(51):15750-1. Epub 2007 Dec 5. PMID:18052280 doi:http://dx.doi.org/10.1021/ja076704r
- ↑ Caines ME, Sorensen JL, Schofield CJ. Structural and mechanistic studies on N(2)-(2-carboxyethyl)arginine synthase. Biochem Biophys Res Commun. 2009 Aug 7;385(4):512-7. Epub 2009 May 27. PMID:19477162 doi:10.1016/j.bbrc.2009.05.095
- ↑ Caines ME, Sorensen JL, Schofield CJ. Structural and mechanistic studies on N(2)-(2-carboxyethyl)arginine synthase. Biochem Biophys Res Commun. 2009 Aug 7;385(4):512-7. Epub 2009 May 27. PMID:19477162 doi:10.1016/j.bbrc.2009.05.095
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