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| | <StructureSection load='2og5' size='340' side='right'caption='[[2og5]], [[Resolution|resolution]] 1.45Å' scene=''> | | <StructureSection load='2og5' size='340' side='right'caption='[[2og5]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2og5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"actinomyces_coelicolor"_(muller_1908)_lieske_1921 "actinomyces coelicolor" (muller 1908) lieske 1921]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OG5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2og5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor Streptomyces coelicolor]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OG5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.45Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">sco3236 (asnO) ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1902 "Actinomyces coelicolor" (Muller 1908) Lieske 1921])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=2og5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2og5 OCA], [https://pdbe.org/2og5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2og5 RCSB], [https://www.ebi.ac.uk/pdbsum/2og5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2og5 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=2og5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2og5 OCA], [https://pdbe.org/2og5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2og5 RCSB], [https://www.ebi.ac.uk/pdbsum/2og5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2og5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ASNO_STRCO ASNO_STRCO]] Catalyzes the 3-hydroxylation of L-asparagine to (2S,3S)-3-hydroxyasparagine. The 3-hydroxylated asparagine produced is incorporated at position 9 during the biosynthesis of the non-ribosomally synthesized calcium-dependent antibiotic (CDA), a 11-residue acidic lipopeptide lactone. Is able to hydroxylate only free L-asparagine, since it hydroxylates neither a CDA analog with unmodified Asn at position 9 nor a peptidyl-carrier-protein (PCP)-bound asparagine. Is not active toward D-asparagine.<ref>PMID:17322197</ref> <ref>PMID:17373765</ref>
| + | [https://www.uniprot.org/uniprot/ASNO_STRCO ASNO_STRCO] Catalyzes the 3-hydroxylation of L-asparagine to (2S,3S)-3-hydroxyasparagine. The 3-hydroxylated asparagine produced is incorporated at position 9 during the biosynthesis of the non-ribosomally synthesized calcium-dependent antibiotic (CDA), a 11-residue acidic lipopeptide lactone. Is able to hydroxylate only free L-asparagine, since it hydroxylates neither a CDA analog with unmodified Asn at position 9 nor a peptidyl-carrier-protein (PCP)-bound asparagine. Is not active toward D-asparagine.<ref>PMID:17322197</ref> <ref>PMID:17373765</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Essen, L O]] | + | [[Category: Streptomyces coelicolor]] |
| - | [[Category: Strieker, M]] | + | [[Category: Essen LO]] |
| - | [[Category: Beta-hydroxylation of amino acid]] | + | [[Category: Strieker M]] |
| - | [[Category: Jelly-roll fold]]
| + | |
| - | [[Category: Non-ribosomal peptide synthesis]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
ASNO_STRCO Catalyzes the 3-hydroxylation of L-asparagine to (2S,3S)-3-hydroxyasparagine. The 3-hydroxylated asparagine produced is incorporated at position 9 during the biosynthesis of the non-ribosomally synthesized calcium-dependent antibiotic (CDA), a 11-residue acidic lipopeptide lactone. Is able to hydroxylate only free L-asparagine, since it hydroxylates neither a CDA analog with unmodified Asn at position 9 nor a peptidyl-carrier-protein (PCP)-bound asparagine. Is not active toward D-asparagine.[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
Non-ribosomally synthesized lipopeptide antibiotics of the daptomycin type are known to contain unnatural beta-modified amino acids, which are essential for bioactivity. Here we present the biochemical and structural basis for the incorporation of 3-hydroxyasparagine at position 9 in the 11-residue acidic lipopeptide lactone calcium-dependent antibiotic (CDA). Direct hydroxylation of l-asparagine by AsnO, a non-heme Fe(2+)/alpha-ketoglutarate-dependent oxygenase encoded by the CDA biosynthesis gene cluster, was validated by Fmoc derivatization of the reaction product and LC/MS analysis. The 1.45, 1.92, and 1.66 A crystal structures of AsnO as apoprotein, Fe(2+) complex, and product complex, respectively, with (2S,3S)-3-hydroxyasparagine and succinate revealed the stereoselectivity and substrate specificity of AsnO. The comparison of native and product-complex structures of AsnO showed a lid-like region (residues F208-E223) that seals the active site upon substrate binding and shields it from sterically demanding peptide substrates. Accordingly, beta-hydroxylated asparagine is synthesized prior to its incorporation into the growing CDA peptide. The AsnO structure could serve as a template for engineering novel enzymes for the synthesis of beta-hydroxylated amino acids.
Mechanistic and structural basis of stereospecific Cbeta-hydroxylation in calcium-dependent antibiotic, a daptomycin-type lipopeptide.,Strieker M, Kopp F, Mahlert C, Essen LO, Marahiel MA ACS Chem Biol. 2007 Mar 20;2(3):187-96. PMID:17373765[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Neary JM, Powell A, Gordon L, Milne C, Flett F, Wilkinson B, Smith CP, Micklefield J. An asparagine oxygenase (AsnO) and a 3-hydroxyasparaginyl phosphotransferase (HasP) are involved in the biosynthesis of calcium-dependent lipopeptide antibiotics. Microbiology. 2007 Mar;153(Pt 3):768-76. PMID:17322197 doi:http://dx.doi.org/153/3/768
- ↑ Strieker M, Kopp F, Mahlert C, Essen LO, Marahiel MA. Mechanistic and structural basis of stereospecific Cbeta-hydroxylation in calcium-dependent antibiotic, a daptomycin-type lipopeptide. ACS Chem Biol. 2007 Mar 20;2(3):187-96. PMID:17373765 doi:10.1021/cb700012y
- ↑ Strieker M, Kopp F, Mahlert C, Essen LO, Marahiel MA. Mechanistic and structural basis of stereospecific Cbeta-hydroxylation in calcium-dependent antibiotic, a daptomycin-type lipopeptide. ACS Chem Biol. 2007 Mar 20;2(3):187-96. PMID:17373765 doi:10.1021/cb700012y
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