|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Solution conformation of cytochrome P450 MycG with mycinamicin IV bound== | | ==Solution conformation of cytochrome P450 MycG with mycinamicin IV bound== |
| - | <StructureSection load='5uhu' size='340' side='right'caption='[[5uhu]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='5uhu' size='340' side='right'caption='[[5uhu]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5uhu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/'micromonospora_griseorubida' 'micromonospora griseorubida']. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UHU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5uhu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Micromonospora_griseorubida Micromonospora griseorubida]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UHU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MIV:MYCINAMICIN+IV'>MIV</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2y98|2y98]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MIV:MYCINAMICIN+IV'>MIV</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mycG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=28040 'Micromonospora griseorubida'])</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=5uhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uhu OCA], [https://pdbe.org/5uhu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uhu RCSB], [https://www.ebi.ac.uk/pdbsum/5uhu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uhu ProSAT]</span></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=5uhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uhu OCA], [http://pdbe.org/5uhu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uhu RCSB], [http://www.ebi.ac.uk/pdbsum/5uhu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uhu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | MycG is a P450 monooxygenase that catalyzes the sequential hydroxylation and epoxidation of mycinamicin IV (M-IV), the last two steps in the biosynthesis of mycinamicin II, a macrolide antibiotic isolated from Micromonospora griseorubida. The crystal structure of MycG with M-IV bound was previously determined but showed the bound substrate in an orientation that did not rationalize the observed regiochemistry of M-IV hydroxylation. Nuclear magnetic resonance paramagnetic relaxation enhancements provided evidence of an orientation of M-IV in the MycG active site more compatible with the observed chemistry, but substrate-induced changes in the enzyme structure were not characterized. We now describe the use of amide 1H-15N residual dipolar couplings as experimental restraints in solvated "soft annealing" molecular dynamics simulations to generate solution structural ensembles of M-IV-bound MycG. Chemical shift perturbations, hydrogen-deuterium exchange, and 15N relaxation behavior provide insight into the dynamic and electronic perturbations in the MycG structure in response to M-IV binding. The solution and crystallographic structures are compared, and the possibility that the crystallographic orientation of bound M-IV represents an inhibitory mode is discussed.
| + | |
| - | | + | |
| - | Solution Conformations and Dynamics of Substrate-Bound Cytochrome P450 MycG.,Tietz DR, Podust LM, Sherman DH, Pochapsky TC Biochemistry. 2017 May 30;56(21):2701-2714. doi: 10.1021/acs.biochem.7b00291., Epub 2017 May 16. PMID:28488849<ref>PMID:28488849</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5uhu" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Micromonospora griseorubida]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pochapsky, T C]] | + | [[Category: Micromonospora griseorubida]] |
| - | [[Category: Tietz, D R]] | + | [[Category: Pochapsky TC]] |
| - | [[Category: Antibiotic biosynthesis]] | + | [[Category: Tietz DR]] |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
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.[1] [2] [3]
References
- ↑ Anzai Y, Li S, Chaulagain MR, Kinoshita K, Kato F, Montgomery J, Sherman DH. Functional analysis of MycCI and MycG, cytochrome P450 enzymes involved in biosynthesis of mycinamicin macrolide antibiotics. Chem Biol. 2008 Sep 22;15(9):950-9. doi: 10.1016/j.chembiol.2008.07.014. PMID:18804032 doi:http://dx.doi.org/10.1016/j.chembiol.2008.07.014
- ↑ Anzai Y, Tsukada S, Sakai A, Masuda R, Harada C, Domeki A, Li S, Kinoshita K, Sherman DH, Kato F. Function of cytochrome P450 enzymes MycCI and MycG in Micromonospora griseorubida, a producer of the macrolide antibiotic mycinamicin. Antimicrob Agents Chemother. 2012 Jul;56(7):3648-56. doi: 10.1128/AAC.06063-11., Epub 2012 Apr 30. PMID:22547618 doi:http://dx.doi.org/10.1128/AAC.06063-11
- ↑ Inouye M, Takada Y, Muto N, Beppu T, Horinouchi S. Characterization and expression of a P-450-like mycinamicin biosynthesis gene using a novel Micromonospora-Escherichia coli shuttle cosmid vector. Mol Gen Genet. 1994 Nov 15;245(4):456-64. PMID:7808395
|
