3t4h: Difference between revisions

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-[[Image:3t4h.png|left|200px]]
+==Crystal Structure of AlkB in complex with Fe(III) and N-Oxalyl-S-(3-nitrobenzyl)-L-cysteine==
+<StructureSection load='3t4h' size='340' side='right' caption='[[3t4h]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3t4h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T4H FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=MD5:N-(CARBOXYCARBONYL)-S-(3-NITROBENZYL)-L-CYSTEINE'>MD5</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fd8|2fd8]], [[2fdf|2fdf]], [[2fdg|2fdg]], [[2fdh|2fdh]], [[2fdi|2fdi]], [[2fdj|2fdj]], [[2fdk|2fdk]], [[3bi3|3bi3]], [[3bie|3bie]], [[3bkz|3bkz]], [[3h8o|3h8o]], [[3h8r|3h8r]], [[3h8x|3h8x]], [[3i2o|3i2o]], [[3i3m|3i3m]], [[3i3q|3i3q]], [[3i49|3i49]], [[3khb|3khb]], [[3khc|3khc]], [[3o1m|3o1m]], [[3o1o|3o1o]], [[3o1p|3o1p]], [[3o1r|3o1r]], [[3o1s|3o1s]], [[3o1t|3o1t]], [[3o1u|3o1u]], [[3o1v|3o1v]], [[3t3y|3t3y]], [[3t4v|3t4v]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">aidD, alkB, b2212, JW2200 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</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=3t4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t4h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3t4h RCSB], [http://www.ebi.ac.uk/pdbsum/3t4h PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI]] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+-Oxoglutarate-dependent nucleic acid demethylases are of biological interest because of their roles in nucleic acid repair and modification. Although some of these enzymes are linked to physiology, their regulatory roles are unclear. Hence, there is a desire to develop selective inhibitors for them; we report studies on AlkB, which reveal it as being amenable to selective inhibition by small molecules. Dynamic combinatorial chemistry linked to mass spectrometric analyses (DCMS) led to the identification of lead compounds, one of which was analyzed by crystallography. Subsequent structure-guided studies led to the identification of inhibitors of improved potency, some of which were shown to be selective over two other 2OG oxygenases. The work further validates the use of the DCMS method and will help to enable the development of inhibitors of nucleic acid modifying 2OG oxygenases both for use as functional probes and, in the longer term, for potential therapeutic use.
-<!--
+Dynamic Combinatorial Mass Spectrometry Leads to Inhibitors of a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase.,Woon EC, Demetriades M, Bagg EA, Aik W, Krylova SM, Ma JH, Chan M, Walport LJ, Wegman DW, Dack KN, McDonough MA, Krylov SN, Schofield CJ J Med Chem. 2012 Feb 22. PMID:22263962<ref>PMID:22263962</ref>
-The line below this paragraph, containing "STRUCTURE_3t4h", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_3t4h|  PDB=3t4h  |  SCENE=  }}
-===Crystal Structure of AlkB in complex with Fe(III) and N-Oxalyl-S-(3-nitrobenzyl)-L-cysteine===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+==See Also==
-<!--
+*[[Dioxygenase|Dioxygenase]]
-The line below this paragraph, {{ABSTRACT_PUBMED_22263962}}, adds the Publication Abstract to the page
+== References ==
-(as it appears on PubMed at http://www.pubmed.gov), where 22263962 is the PubMed ID number.
+<references/>
--->
+__TOC__
-{{ABSTRACT_PUBMED_22263962}}
+</StructureSection>
-==About this Structure==
-[[3t4h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4H OCA].
-==Reference==
-<ref group="xtra">PMID:022263962</ref><references group="xtra"/>
 [[Category: Escherichia coli]]
-[[Category: Aik, W S.]]
+[[Category: Aik, W S]]
-[[Category: Ma, J.]]
+[[Category: Ma, J]]
-[[Category: McDonough, M A.]]
+[[Category: McDonough, M A]]
-[[Category: Schofield, C J.]]
+[[Category: Schofield, C J]]
 [[Category: Double-stranded beta-helix]]
 [[Category: Nucleic acid demethylase]]
 [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]