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.


1m0e

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="1m0e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m0e, resolution 2.50&Aring;" /> '''ZEBULARINE: A NOVEL ...)
Current revision (08:29, 10 April 2024) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1m0e.gif|left|200px]]<br /><applet load="1m0e" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1m0e, resolution 2.50&Aring;" />
 
-
'''ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE'''<br />
 
-
==Overview==
+
==ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE==
-
Mechanism-based inhibitors of enzymes, which mimic reactive intermediates, in the reaction pathway, have been deployed extensively in the analysis of, metabolic pathways and as candidate drugs. The inhibition of, cytosine-[C5]-specific DNA methyltransferases (C5 MTases) by, oligodeoxynucleotides containing 5-azadeoxycytidine (AzadC) and, 5-fluorodeoxycytidine (FdC) provides a well-documented example of, mechanism-based inhibition of enzymes central to nucleic acid metabolism., Here, we describe the interaction between the C5 MTase from Haemophilus, haemolyticus (M.HhaI) and an oligodeoxynucleotide duplex containing 2-H, pyrimidinone, an analogue often referred to as zebularine and known to, give rise to high-affinity complexes with MTases. X-ray crystallography, has demonstrated the formation of a covalent bond between M.HhaI and the, 2-H pyrimidinone-containing oligodeoxynucleotide. This observation enables, a comparison between the mechanisms of action of 2-H pyrimidinone with, other mechanism-based inhibitors such as FdC. This novel complex provides, a molecular explanation for the mechanism of action of the anti-cancer, drug zebularine.
+
<StructureSection load='1m0e' size='340' side='right'caption='[[1m0e]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1m0e]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemophilus_haemolyticus Haemophilus haemolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M0E FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=Z:1-(2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYL)PYRIMIDIN-2(1H)-ONE'>Z</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=1m0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m0e OCA], [https://pdbe.org/1m0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m0e RCSB], [https://www.ebi.ac.uk/pdbsum/1m0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m0e ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/MTH1_HAEPH MTH1_HAEPH] This methylase recognizes the double-stranded sequence GCGC, causes specific methylation on C-2 on both strands, and protects the DNA from cleavage by the HhaI endonuclease.
 +
== 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/m0/1m0e_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</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=1m0e ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
1M0E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Haemophilus_haemolyticus Haemophilus haemolyticus] with SAH as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Deleted_entry Deleted entry], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.73 2.1.1.73] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1M0E OCA].
+
*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
-
 
+
__TOC__
-
==Reference==
+
</StructureSection>
-
Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases., Zhou L, Cheng X, Connolly BA, Dickman MJ, Hurd PJ, Hornby DP, J Mol Biol. 2002 Aug 23;321(4):591-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12206775 12206775]
+
-
[[Category: Deleted entry]]
+
[[Category: Haemophilus haemolyticus]]
[[Category: Haemophilus haemolyticus]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Cheng, X.]]
+
[[Category: Cheng X]]
-
[[Category: Connolly, B.A.]]
+
[[Category: Connolly BA]]
-
[[Category: Dickman, M.J.]]
+
[[Category: Dickman MJ]]
-
[[Category: Hornby, D.P.]]
+
[[Category: Hornby DP]]
-
[[Category: Hurd, P.J.]]
+
[[Category: Hurd PJ]]
-
[[Category: Zhou, L.]]
+
[[Category: Zhou L]]
-
[[Category: SAH]]
+
-
[[Category: mechanism based dna methylation inhibitors]]
+
-
[[Category: protein-dna covalent complex]]
+
-
[[Category: zebularine]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:01:54 2007''
+

Current revision

ZEBULARINE: A NOVEL DNA METHYLATION INHIBITOR THAT FORMS A COVALENT COMPLEX WITH DNA METHYLTRANSFERASE

PDB ID 1m0e

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/1m0e"
Personal tools