4xcb: Difference between revisions
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==Crystal Structure of HygX from Streptomyces hygroscopicus with nickel, 2-oxoglutarate, and hygromycin B bound== | ==Crystal Structure of HygX from Streptomyces hygroscopicus with nickel, 2-oxoglutarate, and hygromycin B bound== | ||
<StructureSection load='4xcb' size='340' side='right' caption='[[4xcb]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='4xcb' size='340' side='right'caption='[[4xcb]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4xcb]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XCB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XCB FirstGlance]. <br> | <table><tr><td colspan='2'>[[4xcb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_hygroscopicus_subsp._hygroscopicus Streptomyces hygroscopicus subsp. hygroscopicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XCB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XCB FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=HY0:HYGROMYCIN+B+VARIANT'>HY0</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=HY0:HYGROMYCIN+B+VARIANT'>HY0</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=4xcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xcb OCA], [http://pdbe.org/4xcb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xcb RCSB], [http://www.ebi.ac.uk/pdbsum/4xcb PDBsum]</span></td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hygX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=68042 Streptomyces hygroscopicus subsp. hygroscopicus])</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=4xcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xcb OCA], [http://pdbe.org/4xcb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xcb RCSB], [http://www.ebi.ac.uk/pdbsum/4xcb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xcb ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Streptomyces hygroscopicus subsp. hygroscopicus]] | |||
[[Category: Bachmann, B O]] | [[Category: Bachmann, B O]] | ||
[[Category: Du, Y]] | [[Category: Du, Y]] | ||
Revision as of 10:09, 29 May 2019
Crystal Structure of HygX from Streptomyces hygroscopicus with nickel, 2-oxoglutarate, and hygromycin B boundCrystal Structure of HygX from Streptomyces hygroscopicus with nickel, 2-oxoglutarate, and hygromycin B bound
Structural highlights
Publication Abstract from PubMedOrthosomycins are oligosaccharide antibiotics that include avilamycin, everninomicin, and hygromycin B and are hallmarked by a rigidifying interglycosidic spirocyclic ortho-delta-lactone (orthoester) linkage between at least one pair of carbohydrates. A subset of orthosomycins additionally contain a carbohydrate capped by a methylenedioxy bridge. The orthoester linkage is necessary for antibiotic activity but rarely observed in natural products. Orthoester linkage and methylenedioxy bridge biosynthesis require similar oxidative cyclizations adjacent to a sugar ring. We have identified a conserved group of nonheme iron, alpha-ketoglutarate-dependent oxygenases likely responsible for this chemistry. High-resolution crystal structures of the EvdO1 and EvdO2 oxygenases of everninomicin biosynthesis, the AviO1 oxygenase of avilamycin biosynthesis, and HygX of hygromycin B biosynthesis show how these enzymes accommodate large substrates, a challenge that requires a variation in metal coordination in HygX. Excitingly, the ternary complex of HygX with cosubstrate alpha-ketoglutarate and putative product hygromycin B identified an orientation of one glycosidic linkage of hygromycin B consistent with metal-catalyzed hydrogen atom abstraction from substrate. These structural results are complemented by gene disruption of the oxygenases evdO1 and evdMO1 from the everninomicin biosynthetic cluster, which demonstrate that functional oxygenase activity is critical for antibiotic production. Our data therefore support a role for these enzymes in the production of key features of the orthosomycin antibiotics. Oxidative cyclizations in orthosomycin biosynthesis expand the known chemistry of an oxygenase superfamily.,McCulloch KM, McCranie EK, Smith JA, Sarwar M, Mathieu JL, Gitschlag BL, Du Y, Bachmann BO, Iverson TM Proc Natl Acad Sci U S A. 2015 Aug 3. pii: 201500964. PMID:26240321[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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