2og7

From Proteopedia

(Difference between revisions)

Current revision

Cystal structure of asparagine oxygenase in complex with Fe(II), 2S,3S-3-hydroxyasparagine and succinate

Structural highlights

2og7 is a 1 chain structure with sequence from Streptomyces coelicolor A3(2). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.66Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2og7"

Categories: Large Structures | Essen L-O | Strieker M

@@ Line 1: / Line 1: @@
-[[Image:2og7.gif|left|200px]]<br /><applet load="2og7" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2og7, resolution 1.660&Aring;" />
-'''Cystal structure of asparagine oxygenase in complex with Fe(II), 2S,3S-3-hydroxyasparagine and succinate'''<br />
-==Overview==
+==Cystal structure of asparagine oxygenase in complex with Fe(II), 2S,3S-3-hydroxyasparagine and succinate==
-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.
+<StructureSection load='2og7' size='340' side='right'caption='[[2og7]], [[Resolution|resolution]] 1.66&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2og7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor_A3(2) Streptomyces coelicolor A3(2)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OG7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OG7 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]] 1.66&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AHB:BETA-HYDROXYASPARAGINE'>AHB</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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=2og7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2og7 OCA], [https://pdbe.org/2og7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2og7 RCSB], [https://www.ebi.ac.uk/pdbsum/2og7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2og7 ProSAT]</span></td></tr>
+</table>
+== 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>
+== 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/og/2og7_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=2og7 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== 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.
-==About this Structure==
+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<ref>PMID:17373765</ref>
-OG7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacteria Bacteria] with <scene name='pdbligand=FE2:'>FE2</scene> and <scene name='pdbligand=SIN:'>SIN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OG7 OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17373765 17373765]
+</div>
-[[Category: Bacteria]]
+<div class="pdbe-citations 2og7" style="background-color:#fffaf0;"></div>
-[[Category: Single protein]]
+== References ==
-[[Category: Essen, L.O.]]
+<references/>
-[[Category: Strieker, M.]]
+__TOC__
-[[Category: FE2]]
+</StructureSection>
-[[Category: SIN]]
+[[Category: Large Structures]]
-[[Category: nonribosomal peptide synthesis; non-heme iron(ii); alpha-ketoglutarate oxygenase; beta-hydroxylated amino acid]]
+[[Category: Essen L-O]]
+[[Category: Strieker M]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 21:10:35 2008''

2og7

From Proteopedia

Current revision

Cystal structure of asparagine oxygenase in complex with Fe(II), 2S,3S-3-hydroxyasparagine and succinate

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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