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6qdx

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Structure of E.coli RlmJ in complex with a bisubstrate analogue (BA4)

Structural highlights

6qdx is a 4 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RLMJ_ECOLI Specifically methylates the adenine in position 2030 of 23S rRNA. Nascent 23S rRNA seems to be the natural substrate. Appears to be not necessary for ribosome assembly. Seems to be required for the utilization of extracellular DNA as the sole source of carbon and energy.^[1] ^[2]

Publication Abstract from PubMed

RNA methyltransferases (MTases) catalyse the transfer of a methyl group to their RNA substrates using most-often S-adenosyl-L-methionine (SAM) as cofactor. Only few RNA-bound MTases structures are currently available due to the difficulties in crystallising RNA:protein complexes. The lack of complex structures results in poorly understood RNA recognition patterns and methylation reaction mechanisms. On the contrary, many cofactor-bound MTase structures are available, resulting in well-understood protein:cofactor recognition, that can guide the design of bisubstrate analogues that mimic the state at which both the substrate and the cofactor is bound. Such bisubstrate analogues were recently synthesized for proteins monomethylating the N6-atom of adenine (m(6)A). These proteins include, amongst others, RlmJ in E. coli and METLL3:METT14 and METTL16 in human. As a proof-of-concept, we here test the ability of the bisubstrate analogues to mimic the substrate:cofactor bound state during catalysis by studying their binding to RlmJ using differential scanning fluorimetry, isothermal titration calorimetry and X-ray crystallography. We find that the methylated adenine base binds in the correct pocket, and thus these analogues could potentially be used broadly to study the RNA recognition and catalytic mechanism of m(6)A MTases. Two bisubstrate analogues bind RlmJ with micro-molar affinity, and could serve as starting scaffolds for inhibitor design against m(6)A RNA MTases. The same analogues cause changes in the melting temperature of the m(1)A RNA MTase, TrmK, indicating non-selective protein:compound complex formation. Thus, optimization of these molecular scaffolds for m(6)A RNA MTase inhibition should aim to increase selectivity, as well as affinity.

Bisubstrate analogues as structural tools to investigate m(6)A methyltransferase active sites.,Oerum S, Catala M, Atdjian C, Brachet F, Ponchon L, Barraud P, Iannazzo L, Droogmans L, Braud E, Etheve-Quelquejeu M, Tisne C RNA Biol. 2019 Mar 17:1-11. doi: 10.1080/15476286.2019.1589360. PMID:30879411^[3]

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

References

↑ Palchevskiy V, Finkel SE. Escherichia coli competence gene homologs are essential for competitive fitness and the use of DNA as a nutrient. J Bacteriol. 2006 Jun;188(11):3902-10. PMID:16707682 doi:10.1128/JB.01974-05
↑ Golovina AY, Dzama MM, Osterman IA, Sergiev PV, Serebryakova MV, Bogdanov AA, Dontsova OA. The last rRNA methyltransferase of E. coli revealed: the yhiR gene encodes adenine-N6 methyltransferase specific for modification of A2030 of 23S ribosomal RNA. RNA. 2012 Sep;18(9):1725-34. doi: 10.1261/rna.034207.112. Epub 2012 Jul 30. PMID:22847818 doi:10.1261/rna.034207.112
↑ Oerum S, Catala M, Atdjian C, Brachet F, Ponchon L, Barraud P, Iannazzo L, Droogmans L, Braud E, Etheve-Quelquejeu M, Tisne C. Bisubstrate analogues as structural tools to investigate m(6)A methyltransferase active sites. RNA Biol. 2019 Mar 17:1-11. doi: 10.1080/15476286.2019.1589360. PMID:30879411 doi:http://dx.doi.org/10.1080/15476286.2019.1589360

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/6qdx"

@@ Line 3: / Line 3: @@
 <StructureSection load='6qdx' size='340' side='right'caption='[[6qdx]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6qdx]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QDX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QDX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6qdx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QDX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QDX FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HY8:(2~{S})-4-[[(2~{S},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl-[3-[[9-[(2~{S},3~{R},4~{S},5~{S})-5-(hydroxymethyl)-3,4-bis(oxidanyl)oxolan-2-yl]purin-6-yl]amino]propyl]amino]-2-azanyl-butanoic+acid'>HY8</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]] 2.1&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/23S_rRNA_(adenine(2030)-N(6))-methyltransferase 23S rRNA (adenine(2030)-N(6))-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.266 2.1.1.266] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HY8:(2~{S})-4-[[(2~{S},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl-[3-[[9-[(2~{S},3~{R},4~{S},5~{S})-5-(hydroxymethyl)-3,4-bis(oxidanyl)oxolan-2-yl]purin-6-yl]amino]propyl]amino]-2-azanyl-butanoic+acid'>HY8</scene></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=6qdx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qdx OCA], [http://pdbe.org/6qdx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qdx RCSB], [http://www.ebi.ac.uk/pdbsum/6qdx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qdx ProSAT]</span></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=6qdx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qdx OCA], [https://pdbe.org/6qdx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qdx RCSB], [https://www.ebi.ac.uk/pdbsum/6qdx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qdx ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/A0A0G3KF30_ECOLX A0A0G3KF30_ECOLX]] Specifically methylates the adenine in position 2030 of 23S rRNA.[HAMAP-Rule:MF_00934]
+[https://www.uniprot.org/uniprot/RLMJ_ECOLI RLMJ_ECOLI] Specifically methylates the adenine in position 2030 of 23S rRNA. Nascent 23S rRNA seems to be the natural substrate. Appears to be not necessary for ribosome assembly. Seems to be required for the utilization of extracellular DNA as the sole source of carbon and energy.<ref>PMID:16707682</ref> <ref>PMID:22847818</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Escherichia coli]]
 [[Category: Large Structures]]
-[[Category: Atdjian, C]]
+[[Category: Atdjian C]]
-[[Category: Barraud, P]]
+[[Category: Barraud P]]
-[[Category: Brachet, F]]
+[[Category: Brachet F]]
-[[Category: Braud, E]]
+[[Category: Braud E]]
-[[Category: Catala, M]]
+[[Category: Catala M]]
-[[Category: Droogmans, L]]
+[[Category: Droogmans L]]
-[[Category: Etheve-Quelquejeu, M]]
+[[Category: Etheve-Quelquejeu M]]
-[[Category: Iannazzo, L]]
+[[Category: Iannazzo L]]
-[[Category: Oerum, S]]
+[[Category: Oerum S]]
-[[Category: Ponchon, L]]
+[[Category: Ponchon L]]
-[[Category: Tisne, C]]
+[[Category: Tisne C]]
-[[Category: Inhibitor]]
-[[Category: M1a]]
-[[Category: M6a]]
-[[Category: Methyltransferase]]
-[[Category: Rlmj]]
-[[Category: Rna binding]]
-[[Category: Rna mtase]]
-[[Category: Structure]]
-[[Category: Transferase]]
-[[Category: Transition state analogue]]
-[[Category: Trmk]]

6qdx

From Proteopedia

Current revision

Structure of E.coli RlmJ in complex with a bisubstrate analogue (BA4)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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