4aw3: Difference between revisions
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<StructureSection load='4aw3' size='340' side='right'caption='[[4aw3]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='4aw3' size='340' side='right'caption='[[4aw3]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4aw3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4aw3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Micromonospora_griseorubida Micromonospora griseorubida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AW3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AW3 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MYV:MYCINAMICIN+V'>MYV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MYV:MYCINAMICIN+V'>MYV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4aw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aw3 OCA], [https://pdbe.org/4aw3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aw3 RCSB], [https://www.ebi.ac.uk/pdbsum/4aw3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aw3 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=4aw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aw3 OCA], [https://pdbe.org/4aw3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aw3 RCSB], [https://www.ebi.ac.uk/pdbsum/4aw3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aw3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/MYCG_MICGR MYCG_MICGR] Involved in the biosynthesis of mycinamicin, a 16-membered macrolide antibiotic. Catalyzes consecutive hydroxylation (at C14) and epoxidation (at C12-C13) reactions with mycinamicin IV as initial substrate, leading to mycinamicin II. These reactions require prior dimethylation of 6-deoxyallose to mycinose for effective conversion by the dual function MycG enzyme.<ref>PMID:18804032</ref> <ref>PMID:22547618</ref> <ref>PMID:7808395</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: Large Structures]] | |||
[[Category: Micromonospora griseorubida]] | [[Category: Micromonospora griseorubida]] | ||
[[Category: Anzai Y]] | |||
[[Category: Anzai | [[Category: Kato F]] | ||
[[Category: Kato | [[Category: Kells PM]] | ||
[[Category: Kells | [[Category: Li S]] | ||
[[Category: Li | [[Category: Pochapsky TC]] | ||
[[Category: Pochapsky | [[Category: Podust LM]] | ||
[[Category: Podust | [[Category: Rutaganira FU]] | ||
[[Category: Rutaganira | [[Category: Sherman DH]] | ||
[[Category: Sherman | [[Category: Tietz DR]] | ||
[[Category: Tietz | |||
Latest revision as of 14:36, 20 December 2023
Structure of the mixed-function P450 MycG F286V mutant in complex with mycinamicin V in P1 space groupStructure of the mixed-function P450 MycG F286V mutant in complex with mycinamicin V in P1 space group
Structural highlights
FunctionMYCG_MICGR Involved in the biosynthesis of mycinamicin, a 16-membered macrolide antibiotic. Catalyzes consecutive hydroxylation (at C14) and epoxidation (at C12-C13) reactions with mycinamicin IV as initial substrate, leading to mycinamicin II. These reactions require prior dimethylation of 6-deoxyallose to mycinose for effective conversion by the dual function MycG enzyme.[1] [2] [3] Publication Abstract from PubMedThe majority of characterized cytochrome P450 enzymes in actinomycete secondary metabolic pathways are strictly substrate-, regio- and stereo-specific. Examples of multifunctional biosynthetic cytochromes P450 with broader substrate and regio-specificity are growing in number and are of particular interest for biosynthetic and chemoenzymatic applications. MycG is among the first P450 monooxygenases characterized that catalyzes both hydroxylation and epoxidation reactions in the final biosynthetic steps, leading to oxidative tailoring of the 16-membered ring macrolide antibiotic mycinamicin II (M-II) in the actinomycete Micromonospora griseorubida. The ordering of steps to complete the biosynthetic process involves a complex substrate recognition pattern by the enzyme and interplay between three tailoring modifications: glycosylation, methylation and oxidation. To understand the catalytic properties of MycG, we structurally characterized the ligand-free enzyme and its complexes with three native metabolites. These include substrates mycinamicin IV (M-IV) and V (M-V), and their biosynthetic precursor mycinamicin III (M-III), which carries the monomethoxy sugar javose instead of the dimethoxylated sugar mycinose. The two methoxy groups of mycinose serve as sensors that mediate initial recognition to discriminate between closely related substrates in the post-polyketide oxidative tailoring of mycinamycin metabolites. Since x-ray structures alone did not explain the mechanisms of macrolide hydroxylation and epoxidation, paramagnetic NMR relaxation measurements were conducted. Molecular modeling based on these data indicates that in solution substrate may penetrate the active site sufficiently to place the abstracted hydrogen atom of M-IV within 6 A of the heme iron, and ~4 A of the oxygen of Fe-ligated water. Substrate recognition by the multifunctional cytochrome P450 MycG in mycinamicin hydroxylation and epoxidation reactions.,Li S, Tietz DR, Rutaganira FU, Kells PM, Anzai Y, Kato F, Pochapsky TC, Sherman DH, Podust LM J Biol Chem. 2012 Sep 5. PMID:22952225[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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