7lzd: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
Line 3: Line 3:
<StructureSection load='7lzd' size='340' side='right'caption='[[7lzd]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='7lzd' size='340' side='right'caption='[[7lzd]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7lzd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LZD FirstGlance]. <br>
<table><tr><td colspan='2'>[[7lzd]] is a 1 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=7LZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LZD FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=YHY:N-{3-[4-(dimethylamino)piperidin-1-yl]phenyl}-4-fluoro-7-methyl-1H-indole-2-carboxamide'>YHY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=YHY:N-{3-[4-(dimethylamino)piperidin-1-yl]phenyl}-4-fluoro-7-methyl-1H-indole-2-carboxamide'>YHY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7lzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lzd OCA], [https://pdbe.org/7lzd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lzd RCSB], [https://www.ebi.ac.uk/pdbsum/7lzd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lzd 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=7lzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lzd OCA], [https://pdbe.org/7lzd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lzd RCSB], [https://www.ebi.ac.uk/pdbsum/7lzd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lzd ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/SETD2_HUMAN SETD2_HUMAN]] Histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. Probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. Binds DNA at promoters. May also act as a transcription activator that binds to promoters. Binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.<ref>PMID:16118227</ref>
[https://www.uniprot.org/uniprot/SETD2_HUMAN SETD2_HUMAN] Histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. Probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. Binds DNA at promoters. May also act as a transcription activator that binds to promoters. Binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.<ref>PMID:16118227</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
Line 25: Line 26:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Boriack-Sjodin, P]]
[[Category: Boriack-Sjodin P]]
[[Category: Farrow, N A]]
[[Category: Farrow NA]]
[[Category: Transferase]]

Latest revision as of 19:01, 18 October 2023

Crystal Structure of SETD2 bound to Compound 35Crystal Structure of SETD2 bound to Compound 35

Structural highlights

7lzd is a 1 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 1.8Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SETD2_HUMAN Histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. Probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. Binds DNA at promoters. May also act as a transcription activator that binds to promoters. Binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.[1]

Publication Abstract from PubMed

SET domain-containing protein 2 (SETD2), a histone methyltransferase, has been identified as a target of interest in certain hematological malignancies, including multiple myeloma. This account details the discovery of EPZ-719, a novel and potent SETD2 inhibitor with a high selectivity over other histone methyltransferases. A screening campaign of the Epizyme proprietary histone methyltransferase-biased library identified potential leads based on a 2-amidoindole core. Structure-based drug design (SBDD) and drug metabolism/pharmacokinetics (DMPK) optimization resulted in EPZ-719, an attractive tool compound for the interrogation of SETD2 biology that enables in vivo target validation studies.

Discovery of a First-in-Class Inhibitor of the Histone Methyltransferase SETD2 Suitable for Preclinical Studies.,Lampe JW, Alford JS, Boriak-Sjodin PA, Brach D, Cosmopoulos K, Duncan KW, Eckley ST, Foley MA, Harvey DM, Motwani V, Munchhof MJ, Raimondi A, Riera TV, Tang C, Thomenius MJ, Totman J, Farrow NA ACS Med Chem Lett. 2021 Aug 24;12(10):1539-1545. doi:, 10.1021/acsmedchemlett.1c00272. eCollection 2021 Oct 14. PMID:34671445[2]

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

See Also

References

  1. ↑ Sun XJ, Wei J, Wu XY, Hu M, Wang L, Wang HH, Zhang QH, Chen SJ, Huang QH, Chen Z. Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem. 2005 Oct 21;280(42):35261-71. Epub 2005 Aug 22. PMID:16118227 doi:http://dx.doi.org/M504012200
  2. ↑ Lampe JW, Alford JS, Boriak-Sjodin PA, Brach D, Cosmopoulos K, Duncan KW, Eckley ST, Foley MA, Harvey DM, Motwani V, Munchhof MJ, Raimondi A, Riera TV, Tang C, Thomenius MJ, Totman J, Farrow NA. Discovery of a First-in-Class Inhibitor of the Histone Methyltransferase SETD2 Suitable for Preclinical Studies. ACS Med Chem Lett. 2021 Aug 24;12(10):1539-1545. doi:, 10.1021/acsmedchemlett.1c00272. eCollection 2021 Oct 14. PMID:34671445 doi:http://dx.doi.org/10.1021/acsmedchemlett.1c00272

7lzd, resolution 1.80Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=7lzd&oldid=3914315"