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| | ==Human MALT1 (caspase-IG3) in complex with thioridazine== | | ==Human MALT1 (caspase-IG3) in complex with thioridazine== |
| - | <StructureSection load='4i1r' size='340' side='right' caption='[[4i1r]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4i1r' size='340' side='right'caption='[[4i1r]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4i1r]] is a 1 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=4I1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I1R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4i1r]] 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=4I1R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I1R FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LZU:10-{2-[(2S)-1-METHYLPIPERIDIN-2-YL]ETHYL}-2-(METHYLSULFANYL)-10H-PHENOTHIAZINE'>LZU</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LZU:10-{2-[(2S)-1-METHYLPIPERIDIN-2-YL]ETHYL}-2-(METHYLSULFANYL)-10H-PHENOTHIAZINE'>LZU</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4i1p|4i1p]]</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=4i1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i1r OCA], [https://pdbe.org/4i1r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i1r RCSB], [https://www.ebi.ac.uk/pdbsum/4i1r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i1r ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MALT1, MLT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4i1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i1r OCA], [http://pdbe.org/4i1r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i1r RCSB], [http://www.ebi.ac.uk/pdbsum/4i1r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i1r ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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. | + | [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 == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Hopfner, K P]] | + | [[Category: Large Structures]] |
| - | [[Category: Lammens, K]] | + | [[Category: Hopfner KP]] |
| - | [[Category: Schlauderer, F]] | + | [[Category: Lammens K]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]] | + | [[Category: Schlauderer F]] |
| - | [[Category: Protease]]
| + | |
| Structural highlights
Disease
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
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.[1] [2] [3]
Publication Abstract from PubMed
Second site: In the crystal structure of human MALT1casp-Ig3 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) in complex with the tricyclic phenothiazine derivative thioridazine (violet in the picture), the inhibitor is bound in a hydrophobic pocket far from the active site. This explains the action of phenothiazine derivatives as noncompetitive, reversible inhibitors.
Structural Analysis of Phenothiazine Derivatives as Allosteric Inhibitors of the MALT1 Paracaspase.,Schlauderer F, Lammens K, Nagel D, Vincendeau M, Eitelhuber AC, Verhelst SH, Kling D, Chrusciel A, Ruland J, Krappmann D, Hopfner KP Angew Chem Int Ed Engl. 2013 Aug 14. doi: 10.1002/anie.201304290. PMID:23946259[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M, Nunez G. Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. J Biol Chem. 2001 Jun 1;276(22):19012-9. Epub 2001 Mar 21. PMID:11262391 doi:10.1074/jbc.M009984200
- ↑ Zhou H, Wertz I, O'Rourke K, Ultsch M, Seshagiri S, Eby M, Xiao W, Dixit VM. Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO. Nature. 2004 Jan 8;427(6970):167-71. Epub 2003 Dec 24. PMID:14695475 doi:10.1038/nature02273
- ↑ Rebeaud F, Hailfinger S, Posevitz-Fejfar A, Tapernoux M, Moser R, Rueda D, Gaide O, Guzzardi M, Iancu EM, Rufer N, Fasel N, Thome M. The proteolytic activity of the paracaspase MALT1 is key in T cell activation. Nat Immunol. 2008 Mar;9(3):272-81. doi: 10.1038/ni1568. Epub 2008 Feb 10. PMID:18264101 doi:10.1038/ni1568
- ↑ Schlauderer F, Lammens K, Nagel D, Vincendeau M, Eitelhuber AC, Verhelst SH, Kling D, Chrusciel A, Ruland J, Krappmann D, Hopfner KP. Structural Analysis of Phenothiazine Derivatives as Allosteric Inhibitors of the MALT1 Paracaspase. Angew Chem Int Ed Engl. 2013 Aug 14. doi: 10.1002/anie.201304290. PMID:23946259 doi:10.1002/anie.201304290
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