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3gxo

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Structure of the Mitomycin 7-O-methyltransferase MmcR with bound Mitomycin A

Structural highlights

3gxo is a 4 chain structure with sequence from Streptomyces lavendulae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[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

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mao Y, Varoglu M, Sherman DH. Molecular characterization and analysis of the biosynthetic gene cluster for the antitumor antibiotic mitomycin C from Streptomyces lavendulae NRRL 2564. Chem Biol. 1999 Apr;6(4):251-63. PMID:10099135 doi:10.1016/S1074-5521(99)80040-4
↑ Grüschow S, Chang LC, Mao Y, Sherman DH. Hydroxyquinone O-methylation in mitomycin biosynthesis. J Am Chem Soc. 2007 May 23;129(20):6470-6. PMID:17461583 doi:10.1021/ja0700193
↑ Singh S, Chang A, Goff RD, Bingman CA, Gruschow S, Sherman DH, Phillips GN Jr, Thorson JS. Structural characterization of the mitomycin 7-O-methyltransferase. Proteins. 2011 Mar 22. doi: 10.1002/prot.23040. PMID:21538548 doi:10.1002/prot.23040

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3gxo"

@@ Line 1: / Line 1: @@
 ==Structure of the Mitomycin 7-O-methyltransferase MmcR with bound Mitomycin A==
-<StructureSection load='3gxo' size='340' side='right' caption='[[3gxo]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+<StructureSection load='3gxo' size='340' side='right'caption='[[3gxo]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3gxo]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_lavendulae"_waksman_and_curtis_1916 "actinomyces lavendulae" waksman and curtis 1916]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GXO FirstGlance]. <br>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=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]] 2.3&#8491;</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=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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gwz|3gwz]]</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>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mmcR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1914 "Actinomyces lavendulae" Waksman and Curtis 1916])</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=3gxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gxo OCA], [http://pdbe.org/3gxo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gxo RCSB], [http://www.ebi.ac.uk/pdbsum/3gxo PDBsum], [http://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>
+    <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/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 33: / Line 33: @@
 __TOC__
 </StructureSection>
-[[Category: Actinomyces lavendulae waksman and curtis 1916]]
+[[Category: Large Structures]]
-[[Category: Bingman, C A]]
+[[Category: Streptomyces lavendulae]]
-[[Category: Chang, A]]
+[[Category: Bingman CA]]
-[[Category: Phillips, G N]]
+[[Category: Chang A]]
-[[Category: Singh, S]]
+[[Category: Phillips Jr GN]]
-[[Category: Thorson, J S]]
+[[Category: Singh S]]
-[[Category: Methyltransferase]]
+[[Category: Thorson JS]]
-[[Category: Mitomycin]]
-[[Category: Mmcr]]
-[[Category: S-adenosyl methionine]]
-[[Category: Transferase]]

3gxo

From Proteopedia

Current revision

Structure of the Mitomycin 7-O-methyltransferase MmcR with bound Mitomycin A

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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