1xds

From Proteopedia

(Difference between revisions)

Revision as of 10:57, 11 September 2015

Crystal structure of Aclacinomycin-10-hydroxylase (RdmB) in complex with S-adenosyl-L-methionine (SAM) and 11-deoxy-beta-rhodomycin (DbrA)

Structural highlights

1xds is a 2 chain structure with sequence from Atcc 25489. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	1qzz, 1r00, 1tw3, 1xdu
Gene:	rdmb (ATCC 25489)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[RDMB_STREF] Involved in the biosynthesis of the anthracycline aclacinomycin which is an aromatic polyketide antibiotic that exhibits high cytotoxicity and is widely applied in the chemotherapy of a variety of cancers. In vivo and in vitro, RdmB catalyzes the removal of the carboxylic group from the C-10 position of 15-demethoxyaclacinomycin T coupled to hydroxylation at the same C-10 position. It could also catalyze the removal of the carboxylic group at the C-10 position of 15-demethoxy-epsilon-rhodomycin coupled to hydroxylation at the same C-10 position to yield rhodomycin B. The reaction catalyzes by RdmB is intriguing, since the enzyme does not use any of the cofactors usually associated with hydroxylases such as flavins and/or metal ions to activate molecular oxygen.^[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

Aclacinomycin 10-hydroxylase is a methyltransferase homologue that catalyzes a S-adenosyl-L-methionine (AdoMet)-dependent hydroxylation of the C-10 carbon atom of 15-demethoxy-epsilon-rhodomycin, a step in the biosynthesis of the polyketide antibiotic beta-rhodomycin. S-Adenosyl-L-homocysteine is an inhibitor of the enzyme, whereas the AdoMet analogue sinefungin can act as cofactor, indicating that a positive charge is required for catalysis. 18O2 experiments show that the hydroxyl group is derived from molecular oxygen. The reaction further requires thiol reagents such as glutathione or dithiothreitol. Incubation of the enzyme with substrate in the absence of reductant leads to the accumulation of an intermediate with a molecular mass consistent with a perhydroxy compound. This intermediate is turned into product upon addition of glutathione. The crystal structure of an abortive enzyme-AdoMet product ternary complex reveals large conformational changes consisting of a domain rotation leading to active site closure upon binding of the anthracycline ligand. The data suggest a mechanism where decarboxylation of the substrate results in the formation of a carbanion intermediate, which is stabilized by resonance through the aromatic ring system of the anthracycline substrate. The delocalization of the electrons is facilitated by the positive charge of the cofactor AdoMet. The activation of oxygen and formation of a hydroxyperoxide intermediate occurs in a manner similar to that observed in flavoenzymes. Aclacinomycin-10-hydroxylase is the first example of a AdoMet-dependent hydroxylation reaction, a novel function for this cofactor. The enzyme lacks methyltransferase activity due to the positioning of the AdoMet methyl group unfavorable for a SN2-type methyl transfer to the substrate.

Aclacinomycin 10-hydroxylase is a novel substrate-assisted hydroxylase requiring S-adenosyl-L-methionine as cofactor.,Jansson A, Koskiniemi H, Erola A, Wang J, Mantsala P, Schneider G, Niemi J J Biol Chem. 2005 Feb 4;280(5):3636-44. Epub 2004 Nov 17. PMID:15548527^[3]

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

References

↑ Wang Y, Niemi J, Airas K, Ylihonko K, Hakala J, Mantsala P. Modifications of aclacinomycin T by aclacinomycin methyl esterase (RdmC) and aclacinomycin-10-hydroxylase (RdmB) from Streptomyces purpurascens. Biochim Biophys Acta. 2000 Jul 14;1480(1-2):191-200. PMID:11004563
↑ Jansson A, Koskiniemi H, Erola A, Wang J, Mantsala P, Schneider G, Niemi J. Aclacinomycin 10-hydroxylase is a novel substrate-assisted hydroxylase requiring S-adenosyl-L-methionine as cofactor. J Biol Chem. 2005 Feb 4;280(5):3636-44. Epub 2004 Nov 17. PMID:15548527 doi:10.1074/jbc.M412095200
↑ Jansson A, Koskiniemi H, Erola A, Wang J, Mantsala P, Schneider G, Niemi J. Aclacinomycin 10-hydroxylase is a novel substrate-assisted hydroxylase requiring S-adenosyl-L-methionine as cofactor. J Biol Chem. 2005 Feb 4;280(5):3636-44. Epub 2004 Nov 17. PMID:15548527 doi:10.1074/jbc.M412095200

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/1xds"

@@ Line 2: / Line 2: @@
 <StructureSection load='1xds' size='340' side='right' caption='[[1xds]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1xds]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_purpurascens Streptomyces purpurascens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XDS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1XDS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1xds]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_25489 Atcc 25489]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XDS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1XDS FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DRA:11-DEOXY-BETA-RHODOMYCIN'>DRA</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1qzz|1qzz]], [[1r00|1r00]], [[1tw3|1tw3]], [[1xdu|1xdu]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rdmb ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1924 Streptomyces purpurascens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rdmb ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1924 ATCC 25489])</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=1xds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xds OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1xds RCSB], [http://www.ebi.ac.uk/pdbsum/1xds PDBsum]</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=1xds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xds OCA], [http://pdbe.org/1xds PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xds RCSB], [http://www.ebi.ac.uk/pdbsum/1xds PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/Q54527_9ACTO Q54527_9ACTO]] Involved in the biosynthesis of the anthracycline aclacinomycin which is an aromatic polyketide antibiotic that exhibits high cytotoxicity and is widely applied in the chemotherapy of a variety of cancers. In vivo and in vitro, RdmB catalyzes the removal of the carboxylic group from the C-10 position of 15-demethoxyaclacinomycin T coupled to hydroxylation at the same C-10 position. It could also catalyze the removal of the carboxylic group at the C-10 position of 15-demethoxy-epsilon-rhodomycin coupled to hydroxylation at the same C-10 position to yield rhodomycin B. The reaction catalyzes by RdmB is intriguing, since the enzyme does not use any of the cofactors usually associated with hydroxylases such as flavins and/or metal ions to activate molecular oxygen.<ref>PMID:11004563</ref> <ref>PMID:15548527</ref>
+[[http://www.uniprot.org/uniprot/RDMB_STREF RDMB_STREF]] Involved in the biosynthesis of the anthracycline aclacinomycin which is an aromatic polyketide antibiotic that exhibits high cytotoxicity and is widely applied in the chemotherapy of a variety of cancers. In vivo and in vitro, RdmB catalyzes the removal of the carboxylic group from the C-10 position of 15-demethoxyaclacinomycin T coupled to hydroxylation at the same C-10 position. It could also catalyze the removal of the carboxylic group at the C-10 position of 15-demethoxy-epsilon-rhodomycin coupled to hydroxylation at the same C-10 position to yield rhodomycin B. The reaction catalyzes by RdmB is intriguing, since the enzyme does not use any of the cofactors usually associated with hydroxylases such as flavins and/or metal ions to activate molecular oxygen.<ref>PMID:11004563</ref> <ref>PMID:15548527</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1xds" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Streptomyces purpurascens]]
+[[Category: Atcc 25489]]
 [[Category: Erola, A]]
 [[Category: Jansson, A]]

1xds

From Proteopedia

Revision as of 10:57, 11 September 2015

Crystal structure of Aclacinomycin-10-hydroxylase (RdmB) in complex with S-adenosyl-L-methionine (SAM) and 11-deoxy-beta-rhodomycin (DbrA)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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