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5mw4

From Proteopedia

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Current revision

Crystal structure of Dot1L in complex with inhibitor CPD7 [N-(3-(((R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)(methyl)amino)propyl)-2-(3-(2-chloro-3-(2-methylpyridin-3-yl)benzo[b]thiophen-5-yl)ureido)acetamide]

Structural highlights

5mw4 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.19Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DOT1L_HUMAN Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.

Publication Abstract from PubMed

Misdirected catalytic activity of histone methyltransferase Dot1L is believed to be causative for a subset of highly aggressive acute leukemias. Targeting the catalytic domain of Dot1L represents a potential therapeutic approach for these leukemias. In the context of a comprehensive Dot1L hit finding strategy, a knowledge-based virtual screen of the Dot1L SAM binding pocket led to the discovery of 2, a non-nucleoside fragment mimicking key interactions of SAM bound to Dot1L. Fragment linking of 2 and 3, an induced back pocket binder identified in earlier studies, followed by careful ligand optimization led to the identification of 7, a highly potent, selective and structurally novel Dot1L inhibitor.

Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach.,Mobitz H, Machauer R, Holzer P, Vaupel A, Stauffer F, Ragot C, Caravatti G, Scheufler C, Fernandez C, Hommel U, Tiedt R, Beyer KS, Chen C, Zhu H, Gaul C ACS Med Chem Lett. 2017 Feb 14;8(3):338-343. doi: 10.1021/acsmedchemlett.6b00519., eCollection 2017 Mar 9. PMID:28337327^[1]

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

References

↑ Mobitz H, Machauer R, Holzer P, Vaupel A, Stauffer F, Ragot C, Caravatti G, Scheufler C, Fernandez C, Hommel U, Tiedt R, Beyer KS, Chen C, Zhu H, Gaul C. Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach. ACS Med Chem Lett. 2017 Feb 14;8(3):338-343. doi: 10.1021/acsmedchemlett.6b00519., eCollection 2017 Mar 9. PMID:28337327 doi:http://dx.doi.org/10.1021/acsmedchemlett.6b00519

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mw4"

@@ Line 3: / Line 3: @@
 <StructureSection load='5mw4' size='340' side='right'caption='[[5mw4]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mw4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MW4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MW4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mw4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MW4 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5JU:N~2~-{[2-CHLORO-3-(2-METHYLPYRIDIN-3-YL)-1-BENZOTHIOPHEN-5-YL]CARBAMOYL}-N-(3-{METHYL[(3R)-1-(5H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PIPERIDIN-3-YL]AMINO}PROPYL)GLYCINAMIDE'>5JU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.19&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DOT1L, KIAA1814, KMT4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5JU:N~2~-{[2-CHLORO-3-(2-METHYLPYRIDIN-3-YL)-1-BENZOTHIOPHEN-5-YL]CARBAMOYL}-N-(3-{METHYL[(3R)-1-(5H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PIPERIDIN-3-YL]AMINO}PROPYL)GLYCINAMIDE'>5JU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=5mw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mw4 OCA], [https://pdbe.org/5mw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mw4 RCSB], [https://www.ebi.ac.uk/pdbsum/5mw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mw4 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mw4 OCA], [http://pdbe.org/5mw4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mw4 RCSB], [http://www.ebi.ac.uk/pdbsum/5mw4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mw4 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN]] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.
+[https://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Histone-lysine N-methyltransferase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Be, C]]
+[[Category: Be C]]
-[[Category: Gaul, C]]
+[[Category: Gaul C]]
-[[Category: Koch, E]]
+[[Category: Koch E]]
-[[Category: Moebitz, H]]
+[[Category: Moebitz H]]
-[[Category: Scheufler, C]]
+[[Category: Scheufler C]]
-[[Category: Stauffer, F]]
+[[Category: Stauffer F]]
-[[Category: Complex]]
-[[Category: Inhibitor]]
-[[Category: Methyltransferase]]
-[[Category: Transferase]]

5mw4

From Proteopedia

Current revision

Crystal structure of Dot1L in complex with inhibitor CPD7 [N-(3-(((R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)(methyl)amino)propyl)-2-(3-(2-chloro-3-(2-methylpyridin-3-yl)benzo[b]thiophen-5-yl)ureido)acetamide]

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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