3zn0: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==LSD1-CoREST in complex with PRSFAA peptide== | |||
===LSD1-CoREST in | <StructureSection load='3zn0' size='340' side='right' caption='[[3zn0]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3zn0]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZN0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZN0 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zms|3zms]], [[3zmt|3zmt]], [[3zmu|3zmu]], [[3zmv|3zmv]], [[3zmz|3zmz]], [[3zn1|3zn1]]</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=3zn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zn0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zn0 RCSB], [http://www.ebi.ac.uk/pdbsum/3zn0 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylase LSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminal domain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoREST can bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively charged alpha-helical turn that forms upon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the same binding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitors exhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors of LSD1. | |||
PROTEIN RECOGNITION BY SMALL PEPTIDE REVERSIBLE INHIBITORS OF THE CHROMATIN-MODIFYING LSD1/CoREST LYSINE DEMETHYLASE.,Tortorici M, Borrello MT, Tardugno M, Chiarelli LR, Pilotto S, Ciossani G, Vellore NA, Bailey SG, Cowan J, O'Connell M, Crabb SJ, Packham GK, Mai A, Baron R, Ganesan A, Mattevi A ACS Chem Biol. 2013 May 30. PMID:23721412<ref>PMID:23721412</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Lysine-specific histone demethylase 1|Lysine-specific histone demethylase 1]] | *[[Lysine-specific histone demethylase 1|Lysine-specific histone demethylase 1]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Baron, R | [[Category: Baron, R]] | ||
[[Category: Borrello, M T | [[Category: Borrello, M T]] | ||
[[Category: Chiarelli, L R | [[Category: Chiarelli, L R]] | ||
[[Category: Ciossani, G | [[Category: Ciossani, G]] | ||
[[Category: Connell, M O | [[Category: Connell, M O]] | ||
[[Category: Cowan, J | [[Category: Cowan, J]] | ||
[[Category: Ganesan, A | [[Category: Ganesan, A]] | ||
[[Category: Mai, A | [[Category: Mai, A]] | ||
[[Category: Mattevi, A | [[Category: Mattevi, A]] | ||
[[Category: Pilotto, S | [[Category: Pilotto, S]] | ||
[[Category: Tardugno, M | [[Category: Tardugno, M]] | ||
[[Category: Tortorici, M | [[Category: Tortorici, M]] | ||
[[Category: Vellore, N A | [[Category: Vellore, N A]] | ||
[[Category: Chromatin]] | [[Category: Chromatin]] | ||
[[Category: Demethylase]] | [[Category: Demethylase]] | ||
[[Category: Oxidoreductase-peptide complex]] | [[Category: Oxidoreductase-peptide complex]] | ||
[[Category: Transcription factor]] | [[Category: Transcription factor]] | ||
Revision as of 12:30, 21 December 2014
LSD1-CoREST in complex with PRSFAA peptideLSD1-CoREST in complex with PRSFAA peptide
Structural highlights
Publication Abstract from PubMedThe combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylase LSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminal domain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoREST can bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively charged alpha-helical turn that forms upon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the same binding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitors exhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors of LSD1. PROTEIN RECOGNITION BY SMALL PEPTIDE REVERSIBLE INHIBITORS OF THE CHROMATIN-MODIFYING LSD1/CoREST LYSINE DEMETHYLASE.,Tortorici M, Borrello MT, Tardugno M, Chiarelli LR, Pilotto S, Ciossani G, Vellore NA, Bailey SG, Cowan J, O'Connell M, Crabb SJ, Packham GK, Mai A, Baron R, Ganesan A, Mattevi A ACS Chem Biol. 2013 May 30. PMID:23721412[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||