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==Structure of the Mitomycin 7-O-methyltransferase MmcR with bound Mitomycin A== | |||
<StructureSection load='3gxo' size='340' side='right'caption='[[3gxo]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3gxo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_lavendulae Streptomyces lavendulae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GXO 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MQA:[(1AS,8S,8AR,8BS)-6,8A-DIMETHOXY-5-METHYL-4,7-DIOXO-1,1A,2,4,7,8,8A,8B-OCTAHYDROAZIRENO[2,3 3,4]PYRROLO[1,2-A]INDOL-8-YL]METHYL+CARBAMATE'>MQA</scene>, <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=3gxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gxo OCA], [https://pdbe.org/3gxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gxo RCSB], [https://www.ebi.ac.uk/pdbsum/3gxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gxo ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MMCR_STRLA MMCR_STRLA] Involved in the biosynthesis of the quinone methoxy group present in the mitomycin A and B, which are used as anticancer agents (PubMed:10099135, PubMed:17461583). In vitro, catalyzes the 6-O-methylation of both C9-beta- and C9-alpha-configured 6-hydroxymitomycins via the transfer of the S-methyl group of S-adenosyl-L-methionine (AdoMet) to the 6-demethylmitomycin A and B. It can also use hydroxyquinone as substrate (PubMed:17461583).<ref>PMID:10099135</ref> <ref>PMID:17461583</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/gx/3gxo_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=3gxo ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mitomycins are quinone-containing antibiotics, widely used as antitumor drugs in chemotherapy. Mitomycin-7-O-methyltransferase (MmcR), a key tailoring enzyme involved in the biosynthesis of mitomycin in Streptomyces lavendulae, catalyzes the 7-O-methylation of both C9beta- and C9alpha-configured 7-hydroxymitomycins. We have determined the crystal structures of the MmcR-S-adenosylhomocysteine (SAH) binary complex and MmcR-SAH-mitomycin A (MMA) ternary complex at resolutions of 1.9and 2.3 A, respectively. The study revealed MmcR to adopt a common S-adenosyl-L-methionine-dependent O-methyltransferase fold and the presence of a structurally conserved active site general acid-base pair is consistent with a proton-assisted methyltransfer common to most methyltransferases. Given the importance of C7 alkylation to modulate mitomycin redox potential, this study may also present a template toward the future engineering of catalysts to generate uniquely bioactive mitomycins. Proteins 2011. (c) 2011 Wiley-Liss, Inc. | |||
Structural characterization of the mitomycin 7-O-methyltransferase.,Singh S, Chang A, Goff RD, Bingman CA, Gruschow S, Sherman DH, Phillips GN Jr, Thorson JS Proteins. 2011 Mar 22. doi: 10.1002/prot.23040. PMID:21538548<ref>PMID:21538548</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3gxo" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptomyces lavendulae]] | |||
[[Category: Bingman CA]] | |||
[[Category: Chang A]] | |||
[[Category: Phillips Jr GN]] | |||
[[Category: Singh S]] | |||
[[Category: Thorson JS]] | |||
Latest revision as of 04:52, 21 November 2024
Structure of the Mitomycin 7-O-methyltransferase MmcR with bound Mitomycin AStructure of the Mitomycin 7-O-methyltransferase MmcR with bound Mitomycin A
Structural highlights
FunctionMMCR_STRLA Involved in the biosynthesis of the quinone methoxy group present in the mitomycin A and B, which are used as anticancer agents (PubMed:10099135, PubMed:17461583). In vitro, catalyzes the 6-O-methylation of both C9-beta- and C9-alpha-configured 6-hydroxymitomycins via the transfer of the S-methyl group of S-adenosyl-L-methionine (AdoMet) to the 6-demethylmitomycin A and B. It can also use hydroxyquinone as substrate (PubMed:17461583).[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 PubMedMitomycins are quinone-containing antibiotics, widely used as antitumor drugs in chemotherapy. Mitomycin-7-O-methyltransferase (MmcR), a key tailoring enzyme involved in the biosynthesis of mitomycin in Streptomyces lavendulae, catalyzes the 7-O-methylation of both C9beta- and C9alpha-configured 7-hydroxymitomycins. We have determined the crystal structures of the MmcR-S-adenosylhomocysteine (SAH) binary complex and MmcR-SAH-mitomycin A (MMA) ternary complex at resolutions of 1.9and 2.3 A, respectively. The study revealed MmcR to adopt a common S-adenosyl-L-methionine-dependent O-methyltransferase fold and the presence of a structurally conserved active site general acid-base pair is consistent with a proton-assisted methyltransfer common to most methyltransferases. Given the importance of C7 alkylation to modulate mitomycin redox potential, this study may also present a template toward the future engineering of catalysts to generate uniquely bioactive mitomycins. Proteins 2011. (c) 2011 Wiley-Liss, Inc. Structural characterization of the mitomycin 7-O-methyltransferase.,Singh S, Chang A, Goff RD, Bingman CA, Gruschow S, Sherman DH, Phillips GN Jr, Thorson JS Proteins. 2011 Mar 22. doi: 10.1002/prot.23040. PMID:21538548[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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