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| | ==Crystal Structure of RebM== | | ==Crystal Structure of RebM== |
| - | <StructureSection load='3bus' size='340' side='right' caption='[[3bus]], [[Resolution|resolution]] 2.65Å' scene=''> | + | <StructureSection load='3bus' size='340' side='right'caption='[[3bus]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3bus]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"nocardia_aerocolonigenes"_(shinobu_and_kawato_1960)_pridham_1970 "nocardia aerocolonigenes" (shinobu and kawato 1960) pridham 1970]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BUS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BUS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3bus]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lentzea_aerocolonigenes Lentzea aerocolonigenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BUS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rbmF, rebM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=68170 "Nocardia aerocolonigenes" (Shinobu and Kawato 1960) Pridham 1970])</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=3bus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bus OCA], [https://pdbe.org/3bus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bus RCSB], [https://www.ebi.ac.uk/pdbsum/3bus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bus 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=3bus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bus OCA], [http://pdbe.org/3bus PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bus RCSB], [http://www.ebi.ac.uk/pdbsum/3bus PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3bus ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/REBMT_LENAE REBMT_LENAE] Glycosyl O-methyltransferase that catalyzes the final step in the biosynthesis of rebeccamycin, an indolocarbazole alkaloid that inhibits topoisomerase 1. Has broad substrate specificity and functions as glycosyl O-methyltransferase on a number of rebeccamycin analogs.<ref>PMID:16575939</ref> <ref>PMID:18502766</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bu/3bus_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bu/3bus_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bingman, C A]] | + | [[Category: Large Structures]] |
| - | [[Category: McCoy, J G]] | + | [[Category: Lentzea aerocolonigenes]] |
| - | [[Category: Phillips, G N]] | + | [[Category: Bingman CA]] |
| - | [[Category: Singh, S]] | + | [[Category: McCoy JG]] |
| - | [[Category: Thorson, J S]] | + | [[Category: Phillips Jr GN]] |
| - | [[Category: Methyltransferase]] | + | [[Category: Singh S]] |
| - | [[Category: Rebeccamycin synthesis]] | + | [[Category: Thorson JS]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
REBMT_LENAE Glycosyl O-methyltransferase that catalyzes the final step in the biosynthesis of rebeccamycin, an indolocarbazole alkaloid that inhibits topoisomerase 1. Has broad substrate specificity and functions as glycosyl O-methyltransferase on a number of rebeccamycin analogs.[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
The 2.65-angstroms crystal structure of the rebeccamycin 4'-O-methyltransferase RebM in complex with S-adenosyl-l-homocysteine revealed RebM to adopt a typical S-adenosylmethionine-binding fold of small molecule O-methyltransferases (O-MTases) and display a weak dimerization domain unique to MTases. Using this structure as a basis, the RebM substrate binding model implicated a predominance of nonspecific hydrophobic interactions consistent with the reported ability of RebM to methylate a wide range of indolocarbazole surrogates. This model also illuminated the three putative RebM catalytic residues (His140/141 and Asp166) subsequently found to be highly conserved among sequence-related natural product O-MTases from GC-rich bacteria. Interrogation of these residues via site-directed mutagenesis in RebM demonstrated His140 and Asp166 to be most important for catalysis. This study reveals RebM to be a member of the general acid/base-dependent O-MTases and, as the first crystal structure for a sugar O-MTase, may also present a template toward the future engineering of natural product MTases for combinatorial applications.
Structure and mechanism of the rebeccamycin sugar 4'-O-methyltransferase RebM.,Singh S, McCoy JG, Zhang C, Bingman CA, Phillips GN Jr, Thorson JS J Biol Chem. 2008 Aug 15;283(33):22628-36. Epub 2008 May 23. PMID:18502766[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhang C, Albermann C, Fu X, Peters NR, Chisholm JD, Zhang G, Gilbert EJ, Wang PG, Van Vranken DL, Thorson JS. RebG Chembiochem. 2006 May;7(5):795-804. PMID:16575939 doi:10.1002/cbic.200500504
- ↑ Singh S, McCoy JG, Zhang C, Bingman CA, Phillips GN Jr, Thorson JS. Structure and mechanism of the rebeccamycin sugar 4'-O-methyltransferase RebM. J Biol Chem. 2008 Aug 15;283(33):22628-36. Epub 2008 May 23. PMID:18502766 doi:10.1074/jbc.M800503200
- ↑ Singh S, McCoy JG, Zhang C, Bingman CA, Phillips GN Jr, Thorson JS. Structure and mechanism of the rebeccamycin sugar 4'-O-methyltransferase RebM. J Biol Chem. 2008 Aug 15;283(33):22628-36. Epub 2008 May 23. PMID:18502766 doi:10.1074/jbc.M800503200
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