3bus: Difference between revisions
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==Crystal Structure of RebM== | |||
<StructureSection load='3bus' size='340' side='right'caption='[[3bus]], [[Resolution|resolution]] 2.65Å' scene=''> | |||
== Structural highlights == | |||
<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='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='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='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> | |||
</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 == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<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/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bus ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:18502766</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3bus" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
< | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Lentzea aerocolonigenes]] | ||
[[Category: | [[Category: Bingman CA]] | ||
[[Category: | [[Category: McCoy JG]] | ||
[[Category: | [[Category: Phillips Jr GN]] | ||
[[Category: | [[Category: Singh S]] | ||
[[Category: | [[Category: Thorson JS]] | ||
Latest revision as of 11:50, 30 October 2024
Crystal Structure of RebMCrystal Structure of RebM
Structural highlights
FunctionREBMT_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 PubMedThe 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
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