6zi7: Difference between revisions
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==Crystal structure of OleP-oleandolide(DEO) bound to L-rhamnose== | ==Crystal structure of OleP-oleandolide(DEO) bound to L-rhamnose== | ||
<StructureSection load='6zi7' size='340' side='right'caption='[[6zi7]]' scene=''> | <StructureSection load='6zi7' size='340' side='right'caption='[[6zi7]], [[Resolution|resolution]] 2.28Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZI7 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6zi7]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_antibioticus Streptomyces antibioticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZI7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZI7 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.28Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=QR8:(3~{R},4~{S},5~{R},6~{S},7~{S},9~{S},11~{R},12~{S},13~{R},14~{R})-3,5,7,9,11,13,14-heptamethyl-4,6,12-tris(oxidanyl)-1-oxacyclotetradecane-2,10-dione'>QR8</scene>, <scene name='pdbligand=RAM:ALPHA-L-RHAMNOSE'>RAM</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=6zi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zi7 OCA], [https://pdbe.org/6zi7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zi7 RCSB], [https://www.ebi.ac.uk/pdbsum/6zi7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zi7 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q59819_STRAT Q59819_STRAT] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The cytochrome P450 OleP catalyzes the epoxidation of aliphatic carbons on both the aglycone 8.8a-deoxyoleandolide (DEO) and the monoglycosylated L-olivosyl-8.8a-deoxyoleandolide (L-O-DEO) intermediates of oleandomycin biosynthesis. We investigated the substrate versatility of the enzyme. X-ray and equilibrium binding data show that the aglycone DEO loosely fits the OleP active site, triggering the closure that prepares it for catalysis only on a minor population of enzyme. The open-to-closed state transition allows solvent molecules to accumulate in a cavity that forms upon closure, mediating protein-substrate interactions. In silico docking of the monoglycosylated L-O-DEO in the closed OleP-DEO structure shows that the L-olivosyl moiety can be hosted in the same cavity, replacing solvent molecules and directly contacting structural elements involved in the transition. X-ray structures of aglycone-bound OleP in the presence of L-rhamnose confirm the cavity as a potential site for sugar binding. All considered, we propose L-O-DEO as the optimal substrate of OleP, the L-olivosyl moiety possibly representing the molecular wedge that triggers a more efficient structural response upon substrate binding, favoring and stabilizing the enzyme closure before catalysis. OleP substrate versatility is supported by structural solvent molecules that compensate for the absence of a glycosyl unit when the aglycone is bound. | |||
Dissecting the Cytochrome P450 OleP Substrate Specificity: Evidence for a Preferential Substrate.,Parisi G, Freda I, Exertier C, Cecchetti C, Gugole E, Cerutti G, D'Auria L, Macone A, Vallone B, Savino C, Montemiglio LC Biomolecules. 2020 Oct 6;10(10). pii: biom10101411. doi: 10.3390/biom10101411. PMID:33036250<ref>PMID:33036250</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6zi7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Streptomyces antibioticus]] | |||
[[Category: Freda I]] | [[Category: Freda I]] | ||
[[Category: Montemiglio LC]] | [[Category: Montemiglio LC]] | ||
Latest revision as of 14:52, 1 February 2024
Crystal structure of OleP-oleandolide(DEO) bound to L-rhamnoseCrystal structure of OleP-oleandolide(DEO) bound to L-rhamnose
Structural highlights
FunctionPublication Abstract from PubMedThe cytochrome P450 OleP catalyzes the epoxidation of aliphatic carbons on both the aglycone 8.8a-deoxyoleandolide (DEO) and the monoglycosylated L-olivosyl-8.8a-deoxyoleandolide (L-O-DEO) intermediates of oleandomycin biosynthesis. We investigated the substrate versatility of the enzyme. X-ray and equilibrium binding data show that the aglycone DEO loosely fits the OleP active site, triggering the closure that prepares it for catalysis only on a minor population of enzyme. The open-to-closed state transition allows solvent molecules to accumulate in a cavity that forms upon closure, mediating protein-substrate interactions. In silico docking of the monoglycosylated L-O-DEO in the closed OleP-DEO structure shows that the L-olivosyl moiety can be hosted in the same cavity, replacing solvent molecules and directly contacting structural elements involved in the transition. X-ray structures of aglycone-bound OleP in the presence of L-rhamnose confirm the cavity as a potential site for sugar binding. All considered, we propose L-O-DEO as the optimal substrate of OleP, the L-olivosyl moiety possibly representing the molecular wedge that triggers a more efficient structural response upon substrate binding, favoring and stabilizing the enzyme closure before catalysis. OleP substrate versatility is supported by structural solvent molecules that compensate for the absence of a glycosyl unit when the aglycone is bound. Dissecting the Cytochrome P450 OleP Substrate Specificity: Evidence for a Preferential Substrate.,Parisi G, Freda I, Exertier C, Cecchetti C, Gugole E, Cerutti G, D'Auria L, Macone A, Vallone B, Savino C, Montemiglio LC Biomolecules. 2020 Oct 6;10(10). pii: biom10101411. doi: 10.3390/biom10101411. PMID:33036250[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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