View source for 7pav


==MALT1 in complex with compound 1==
<StructureSection load='7pav' size='340' side='right'caption='[[7pav]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7pav]] 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=7PAV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PAV 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]] 2.199&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6IO:~{N}1,~{N}4-bis[2-(trifluoromethyl)pyrimidin-4-yl]cyclohexane-1,4-diamine'>6IO</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=7pav FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pav OCA], [https://pdbe.org/7pav PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pav RCSB], [https://www.ebi.ac.uk/pdbsum/7pav PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pav ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MALT1_HUMAN MALT1_HUMAN] Note=A chromosomal aberration involving MALT1 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with BIRC2. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.
== Function ==
[https://www.uniprot.org/uniprot/MALT1_HUMAN MALT1_HUMAN] Enhances BCL10-induced activation of NF-kappa-B. Involved in nuclear export of BCL10. Binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity. Has ubiquitin ligase activity. MALT1-dependent BCL10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion.<ref>PMID:11262391</ref> <ref>PMID:14695475</ref> <ref>PMID:18264101</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) is a promising strategy to modulate NF-kappaB signaling, with the potential to treat B-cell lymphoma and autoimmune diseases. We describe the discovery and optimization of (1s,4s)-N,N'-diaryl cyclohexane-1,4-diamines, a novel series of allosteric MALT1 inhibitors, resulting in compound 8 with single digit micromolar cell potency. X-ray analysis confirms that this compound binds to an induced allosteric site in MALT1. Compound 8 is highly selective and has an excellent in vivo rat PK profile with low clearance and high oral bioavailability, making it a promising lead for further optimization.

Discovery and optimization of cyclohexane-1,4-diamines as allosteric MALT1 inhibitors.,Schiesser S, Hajek P, Pople HE, Kack H, Oster L, Cox RJ Eur J Med Chem. 2021 Oct 21;227:113925. doi: 10.1016/j.ejmech.2021.113925. PMID:34742013<ref>PMID:34742013</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7pav" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kack H]]
[[Category: Oster L]]