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| | ==Crystal structure of O-ureido-L-serine-bound K43A mutant of O-ureido-L-serine synthase== | | ==Crystal structure of O-ureido-L-serine-bound K43A mutant of O-ureido-L-serine synthase== |
| - | <StructureSection load='3x44' size='340' side='right' caption='[[3x44]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='3x44' size='340' side='right'caption='[[3x44]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3x44]] is a 2 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=3X44 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3X44 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3x44]] is a 2 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=3X44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3X44 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PUS:(E)-O-(CARBAMOYLAMINO)-N-({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYLIDENE)-L-SERINE'>PUS</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]] 1.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dcsD ([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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PUS:(E)-O-(CARBAMOYLAMINO)-N-({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYLIDENE)-L-SERINE'>PUS</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3x44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3x44 OCA], [http://pdbe.org/3x44 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3x44 RCSB], [http://www.ebi.ac.uk/pdbsum/3x44 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3x44 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=3x44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3x44 OCA], [https://pdbe.org/3x44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3x44 RCSB], [https://www.ebi.ac.uk/pdbsum/3x44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3x44 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DCSD_STRLA DCSD_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 addition of hydroxyurea on O-acetyl-L-serine (OAS) to yield O-ureido-L-serine. It prefers sulfide as the second substrate, followed by hydroxyurea, L-homocysteine, and thiosulfate.<ref>PMID:20086163</ref> <ref>PMID:23529730</ref> | + | [https://www.uniprot.org/uniprot/DCSD_STRLA DCSD_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 addition of hydroxyurea on O-acetyl-L-serine (OAS) to yield O-ureido-L-serine. It prefers sulfide as the second substrate, followed by hydroxyurea, L-homocysteine, and thiosulfate.<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: Matoba, Y]] | + | [[Category: Streptomyces lavendulae]] |
| - | [[Category: Oda, K]] | + | [[Category: Matoba Y]] |
| - | [[Category: Sugiyama, M]] | + | [[Category: Oda K]] |
| - | [[Category: Uda, N]] | + | [[Category: Sugiyama M]] |
| - | [[Category: D-cycloserine]]
| + | [[Category: Uda N]] |
| - | [[Category: Synthase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Type ii plp enzyme]]
| + | |
| Structural highlights
Function
DCSD_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 addition of hydroxyurea on O-acetyl-L-serine (OAS) to yield O-ureido-L-serine. It prefers sulfide as the second substrate, followed by hydroxyurea, L-homocysteine, and thiosulfate.[1] [2]
Publication Abstract from PubMed
We have recently been successful in cloning a gene cluster necessary for the biosynthesis of D-cycloserine (D-CS) from D-CS-producing Streptomyces lavendulae ATCC11924. Although dcsD, one of the open reading frames located on the gene cluster, encodes a protein homologous to O-acetylserine sulfhydrylase that synthesizes L-cysteine using O-acetyl-L-serine together with sulfide, it functions to form O-ureido-L-serine as a D-CS biosynthetic intermediate, using O-acetyl-L-serine together with hydroxyurea (HU). Using crystallographic and mutational studies, three amino acid residues in DcsD that are important for the substrate preference toward HU were determined in the present study. We showed that two of the three residues are important for the binding of HU into the substrate-binding pocket. The other residue contributes to the formation of a loose hydrogen-bond network during the catalytic reaction. Information regarding the amino acid residues will be very useful in designing a new catalyst to synthesize the beta-substituted-L-alanine derivatives. This article is protected by copyright. All rights reserved.
The structural and mutational analyses of O-ureido-L-serine synthase necessary for D-cycloserine biosynthesis.,Uda N, Matoba Y, Oda K, Kumagai T, Sugiyama M FEBS J. 2015 Jul 24. doi: 10.1111/febs.13386. PMID:26207937[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
- ↑ Uda N, Matoba Y, Oda K, Kumagai T, Sugiyama M. The structural and mutational analyses of O-ureido-L-serine synthase necessary for D-cycloserine biosynthesis. FEBS J. 2015 Jul 24. doi: 10.1111/febs.13386. PMID:26207937 doi:http://dx.doi.org/10.1111/febs.13386
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