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| | <StructureSection load='6jil' size='340' side='right'caption='[[6jil]], [[Resolution|resolution]] 2.32Å' scene=''> | | <StructureSection load='6jil' size='340' side='right'caption='[[6jil]], [[Resolution|resolution]] 2.32Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6jil]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_lavendulae"_waksman_and_curtis_1916 "actinomyces lavendulae" waksman and curtis 1916]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JIL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6JIL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6jil]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_lavendulae Streptomyces lavendulae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JIL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</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]] 2.32Å</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=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dcsG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1914 "Actinomyces lavendulae" Waksman and Curtis 1916])</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=6jil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jil OCA], [https://pdbe.org/6jil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jil RCSB], [https://www.ebi.ac.uk/pdbsum/6jil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jil ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/O-ureido-D-serine_cyclo-ligase O-ureido-D-serine cyclo-ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.3.5 6.3.3.5] </span></td></tr> | + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6jil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jil OCA], [http://pdbe.org/6jil PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jil RCSB], [http://www.ebi.ac.uk/pdbsum/6jil PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jil ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DCSG_STRLA DCSG_STRLA]] Involved in the biosynthesis of the antibiotic D-cycloserine (DCS), a cyclic structural analog of D-alanine, used as an antitubercular agent. Catalyzes the synthesis of D-cycloserine from O-ureido-D-serine. It reacts exclusively with O-ureido-D-serine.<ref>PMID:20086163</ref> <ref>PMID:23529730</ref> | + | [https://www.uniprot.org/uniprot/DCSG_STRLA DCSG_STRLA] Involved in the biosynthesis of the antibiotic D-cycloserine (DCS), a cyclic structural analog of D-alanine, used as an antitubercular agent. Catalyzes the synthesis of D-cycloserine from O-ureido-D-serine. It reacts exclusively with O-ureido-D-serine.<ref>PMID:20086163</ref> <ref>PMID:23529730</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Actinomyces lavendulae waksman and curtis 1916]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: O-ureido-D-serine cyclo-ligase]] | + | [[Category: Streptomyces lavendulae]] |
| - | [[Category: Matoba, Y]] | + | [[Category: Matoba Y]] |
| - | [[Category: Sugiyama, M]] | + | [[Category: Sugiyama M]] |
| - | [[Category: Antibiotic]]
| + | |
| - | [[Category: Atp-grasp family]]
| + | |
| - | [[Category: Biosynthesis]]
| + | |
| - | [[Category: Ligase]]
| + | |
| Structural highlights
Function
DCSG_STRLA Involved in the biosynthesis of the antibiotic D-cycloserine (DCS), a cyclic structural analog of D-alanine, used as an antitubercular agent. Catalyzes the synthesis of D-cycloserine from O-ureido-D-serine. It reacts exclusively with O-ureido-D-serine.[1] [2]
Publication Abstract from PubMed
In the biosynthetic pathway of an anti-tubercular antibiotic D-cycloserine (D-CS), O-ureido-D-serine (D-OUS) is converted to D-CS. We have previously demonstrated that DcsG, classified into the ATP-grasp superfamily enzyme, catalyzes the ring formation to generate D-CS, which is accompanied by the cleavage of a bond in the urea moiety of D-OUS to remove a carbamoyl group. Although the general ATP-grasp enzymes catalyze an ATP-dependent ligation reaction between two substrates, DcsG catalyzes specifically the generation of an intramolecular covalent bond. In the present study, cyanate was found in the reaction mixture, suggesting that carbamoyl group is eliminated as an isocyanic acid during the reaction. By the crystallographic and mutational investigations of DcsG, we anticipate the residues necessary for the binding of D-OUS. An acylphosphate intermediate must be bound at the narrow pocket of DcsG in a folded conformation, inducing the bond cleavage and the new bond formation to generate cyanate and D-CS, respectively.
Cyclization mechanism catalyzed by an ATP-grasp enzyme essential for D-cycloserine biosynthesis.,Matoba Y, Uda N, Kudo M, Sugiyama M FEBS J. 2019 Dec 3. doi: 10.1111/febs.15163. PMID:31793174[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kumagai T, Koyama Y, Oda K, Noda M, Matoba Y, Sugiyama M. Molecular cloning and heterologous expression of a biosynthetic gene cluster for the antitubercular agent D-cycloserine produced by Streptomyces lavendulae. Antimicrob Agents Chemother. 2010 Mar;54(3):1132-9. doi: 10.1128/AAC.01226-09., Epub 2010 Jan 19. PMID:20086163 doi:http://dx.doi.org/10.1128/AAC.01226-09
- ↑ Uda N, Matoba Y, Kumagai T, Oda K, Noda M, Sugiyama M. Establishment of an in vitro D-cycloserine-synthesizing system by using O-ureido-L-serine synthase and D-cycloserine synthetase found in the biosynthetic pathway. Antimicrob Agents Chemother. 2013 Jun;57(6):2603-12. doi: 10.1128/AAC.02291-12., Epub 2013 Mar 25. PMID:23529730 doi:http://dx.doi.org/10.1128/AAC.02291-12
- ↑ Matoba Y, Uda N, Kudo M, Sugiyama M. Cyclization mechanism catalyzed by an ATP-grasp enzyme essential for D-cycloserine biosynthesis. FEBS J. 2019 Dec 3. doi: 10.1111/febs.15163. PMID:31793174 doi:http://dx.doi.org/10.1111/febs.15163
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