4r29
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4r29]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R29 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4r29]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R29 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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]] 2.31Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=4r29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r29 OCA], [https://pdbe.org/4r29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r29 RCSB], [https://www.ebi.ac.uk/pdbsum/4r29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r29 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=4r29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r29 OCA], [https://pdbe.org/4r29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r29 RCSB], [https://www.ebi.ac.uk/pdbsum/4r29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r29 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/NLEE_ECO57 NLEE_ECO57] Cysteine methyltransferase effector that inhibits host cell NF-kappa-B activation by preventing nuclear translocation of host protein RELA/p65. Acts by mediating cysteine methylation of host proteins TAB2 and TAB3: methylation of a conserved cysteine residue of the RanBP2-type zinc finger (NZF) of TAB2 and TAB3 disrupts zinc-binding, thereby inactivating the ubiquitin chain-binding activity of TAB2 and TAB3, leading to NF-kappa-B inactivation. Also mediates cysteine methylation of host protein ZRANB3, inactivating its ability to bind ubiquitin chains.[UniProtKB:B7UI22] | [https://www.uniprot.org/uniprot/NLEE_ECO57 NLEE_ECO57] Cysteine methyltransferase effector that inhibits host cell NF-kappa-B activation by preventing nuclear translocation of host protein RELA/p65. Acts by mediating cysteine methylation of host proteins TAB2 and TAB3: methylation of a conserved cysteine residue of the RanBP2-type zinc finger (NZF) of TAB2 and TAB3 disrupts zinc-binding, thereby inactivating the ubiquitin chain-binding activity of TAB2 and TAB3, leading to NF-kappa-B inactivation. Also mediates cysteine methylation of host protein ZRANB3, inactivating its ability to bind ubiquitin chains.[UniProtKB:B7UI22] | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Enteropathogenic E. coli (EPEC) and related enterobacteria rely on a type III secretion system (T3SS) effector NleE to block host NF-kappaB signaling. NleE is a first in class, novel S-adenosyl-L-methionine (SAM)-dependent methyltransferase that methylates a zinc-coordinating cysteine in the Npl4-like Zinc Finger (NZF) domains in TAB2/3 adaptors in the NF-kappaB pathway, but its mechanism of action and other human substrates are unknown. Here we solve crystal structure of NleE-SAM complex, which reveals a methyltransferase fold different from those of known ones. The SAM, cradled snugly at the bottom of a deep and narrow cavity, adopts a unique conformation ready for nucleophilic attack by the methyl acceptor. The substrate NZF domain can be well docked into the cavity, and molecular dynamic simulation indicates that Cys673 in TAB2-NZF is spatially and energetically favorable for attacking the SAM. We further identify a new NleE substrate, ZRANB3, that functions in PCNA binding and remodeling of stalled replication forks at the DNA damage sites. Specific inactivation of the NZF domain in ZRANB3 by NleE offers a unique opportunity to suggest that ZRANB3-NZF domain functions in DNA repair processes other than ZRANB3 recruitment to DNA damage sites. Our analyses suggest a novel and unexpected link between EPEC infection, virulence proteins and genome integrity. | ||
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| - | Structure and Specificity of the Bacterial Cysteine Methyltransferase Effector NleE Suggests a Novel Substrate in Human DNA Repair Pathway.,Yao Q, Zhang L, Wan X, Chen J, Hu L, Ding X, Li L, Karar J, Peng H, Chen S, Huang N, Rauscher FJ 3rd, Shao F PLoS Pathog. 2014 Nov 20;10(11):e1004522. doi: 10.1371/journal.ppat.1004522., eCollection 2014 Nov. PMID:25412445<ref>PMID:25412445</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4r29" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of bacterial cysteine methyltransferase effector NleE
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Categories: Escherichia coli O157:H7 | Large Structures | Chen J | Hu L | Shao F | Yao Q | Zhang L
