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5eeh

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Revision as of 17:03, 15 November 2017

Crystal structure of carminomycin-4-O-methyltransferase DnrK in complex with SAH and 2-chloro-4-nitrophenol

Structural highlights

5eeh is a 3 chain structure with sequence from As 4.1799. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	5eeg
Gene:	dnrK (AS 4.1799)
Activity:	Carminomycin 4-O-methyltransferase, with EC number 2.1.1.292
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DNRK_STRPE] Involved in the biosynthesis of the anthracyclines carminomycin and daunorubicin (daunomycin) which are aromatic polyketide antibiotics that exhibit high cytotoxicity and are widely applied in the chemotherapy of a variety of cancers. In vivo, catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to the 4-O-position of carminomycin to form daunorubicin. In vitro, it also methylates the anthracyclines rhodomycin D (10-carbomethoxy-13-deoxycarminomycin) and 13-deoxy-carminomycin at the 4-hydroxyl position. It is quite specific with respect to the length of the carbohydrate chain at the C7 position, but it can accept substrates with bulky substituent at C10 position.^[1]

Publication Abstract from PubMed

S-adenosyl-L-methionine (AdoMet) is an essential enzyme cosubstrate in fundamental biology with an expanding range of biocatalytic and therapeutic applications. We report the design, synthesis and evaluation of stable, functional AdoMet isosteres that are resistant to the primary contributors to AdoMet degradation (depurination, intramolecular cyclization and sulfonium epimerization). Corresponding biochemical and structural studies demonstrate the AdoMet surrogates to serve as competent enzyme cosubstrates and to bind a prototypical class I model methyltransferase (DnrK) in a manner nearly identical to AdoMet. Given this conservation in function and molecular recognition, the isosteres presented are anticipated to serve as useful surrogates in other AdoMet-dependent processes and may also be resistant to, and/or potentially even inhibit, other therapeutically relevant AdoMet-dependent metabolic transformations (such as the validated drug target AdoMet decarboxylase). This work also highlights the ability of the prototypical class I model methyltransferase DnrK to accept non-native surrogate acceptors as an enabling feature of a new high-throughput methyltransferase assay.

Functional AdoMet isosteres resistant to classical AdoMet degradation pathways.,Huber TD, Wang F, Singh S, Johnson BR, Zhang J, Sunkara M, Van Lanen SG, Morris AJ, Phillips GN, Thorson JS ACS Chem Biol. 2016 Jun 28. PMID:27351335^[2]

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

References

↑ Jansson A, Koskiniemi H, Mantsala P, Niemi J, Schneider G. Crystal structure of a ternary complex of DnrK, a methyltransferase in daunorubicin biosynthesis, with bound products. J Biol Chem. 2004 Sep 24;279(39):41149-56. Epub 2004 Jul 24. PMID:15273252 doi:10.1074/jbc.M407081200
↑ Huber TD, Wang F, Singh S, Johnson BR, Zhang J, Sunkara M, Van Lanen SG, Morris AJ, Phillips GN, Thorson JS. Functional AdoMet isosteres resistant to classical AdoMet degradation pathways. ACS Chem Biol. 2016 Jun 28. PMID:27351335 doi:http://dx.doi.org/10.1021/acschembio.6b00348

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5eeh"

@@ Line 3: / Line 3: @@
 <StructureSection load='5eeh' size='340' side='right' caption='[[5eeh]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5eeh]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EEH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EEH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5eeh]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/As_4.1799 As 4.1799]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EEH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EEH FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P9P:2-CHLORANYL-4-NITRO-PHENOL'>P9P</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5eeg|5eeg]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dnrK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1950 AS 4.1799])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carminomycin_4-O-methyltransferase Carminomycin 4-O-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.292 2.1.1.292] </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=5eeh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eeh OCA], [http://pdbe.org/5eeh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eeh RCSB], [http://www.ebi.ac.uk/pdbsum/5eeh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eeh ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: As 4 1799]]
 [[Category: Carminomycin 4-O-methyltransferase]]
 [[Category: NatPro, Enzyme Discovery for Natural Product Biosynthesis]]

5eeh

From Proteopedia

Revision as of 17:03, 15 November 2017

Crystal structure of carminomycin-4-O-methyltransferase DnrK in complex with SAH and 2-chloro-4-nitrophenol

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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