This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1xds

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:18, 3 April 2024) (edit) (undo)
 
(11 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1xds.gif|left|200px]]
 
-
{{Structure
+
==Crystal structure of Aclacinomycin-10-hydroxylase (RdmB) in complex with S-adenosyl-L-methionine (SAM) and 11-deoxy-beta-rhodomycin (DbrA)==
-
|PDB= 1xds |SIZE=350|CAPTION= <scene name='initialview01'>1xds</scene>, resolution 2.30&Aring;
+
<StructureSection load='1xds' size='340' side='right'caption='[[1xds]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene> and <scene name='pdbligand=DRA:11-DEOXY-BETA-RHODOMYCIN'>DRA</scene>
+
<table><tr><td colspan='2'>[[1xds]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=1XDS FirstGlance]. <br>
-
|ACTIVITY=
+
</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>
-
|GENE= rdmb ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1924 Streptomyces purpurascens])
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DRA:11-DEOXY-BETA-RHODOMYCIN'>DRA</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=1xds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xds OCA], [https://pdbe.org/1xds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xds RCSB], [https://www.ebi.ac.uk/pdbsum/1xds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xds ProSAT]</span></td></tr>
-
 
+
</table>
-
'''Crystal structure of Aclacinomycin-10-hydroxylase (RdmB) in complex with S-adenosyl-L-methionine (SAM) and 11-deoxy-beta-rhodomycin (DbrA)'''
+
== Function ==
-
 
+
[https://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 ==
-
==Overview==
+
[[Image:Consurf_key_small.gif|200px|right]]
-
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.
+
Check<jmol>
-
 
+
<jmolCheckbox>
-
==About this Structure==
+
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xd/1xds_consurf.spt"</scriptWhenChecked>
-
1XDS is a [[Single protein]] structure of 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].
+
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
-
 
+
<text>to colour the structure by Evolutionary Conservation</text>
-
==Reference==
+
</jmolCheckbox>
-
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:[http://www.ncbi.nlm.nih.gov/pubmed/15548527 15548527]
+
</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=1xds ConSurf].
-
[[Category: Single protein]]
+
<div style="clear:both"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Streptomyces purpurascens]]
[[Category: Streptomyces purpurascens]]
-
[[Category: Erola, A.]]
+
[[Category: Erola A]]
-
[[Category: Jansson, A.]]
+
[[Category: Jansson A]]
-
[[Category: Koskiniemi, H.]]
+
[[Category: Koskiniemi H]]
-
[[Category: Mantsala, P.]]
+
[[Category: Mantsala P]]
-
[[Category: Niemi, J.]]
+
[[Category: Niemi J]]
-
[[Category: SPINE, Structural Proteomics in Europe.]]
+
[[Category: Schneider G]]
-
[[Category: Schneider, G.]]
+
[[Category: Wang J]]
-
[[Category: Wang, J.]]
+
-
[[Category: DRA]]
+
-
[[Category: SAM]]
+
-
[[Category: anthracycline; hydroxylase; s-adenosyl-l-methionine; streptomyces; polyketide antibiotics; divergent evolution]]
+
-
[[Category: spine]]
+
-
[[Category: structural genomic]]
+
-
[[Category: structural proteomics in europe]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:08:25 2008''
+

Current revision

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

PDB ID 1xds

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1xds"
Personal tools