7d4o

From Proteopedia

(Difference between revisions)

Current revision

cyclic trinucleotide synthase CdnD in complex with ATP and ADP

Structural highlights

7d4o is a 2 chain structure with sequence from Enterobacter cloacae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.87Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CDND2_ENTCL CBASS (cyclic oligonucleotide-based antiphage signaling system) provides immunity against bacteriophage. The CD-NTase protein synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signals activate a diverse range of effectors, leading to bacterial cell death and thus abortive phage infection. A type II-C(AAG) CBASS system (PubMed:32839535).^[1] ^[2] Cyclic trinucleotide synthase that catalyzes the synthesis of 3',3',3'-cyclic AMP-AMP-GMP as the major product, a second messenger for cell signal transduction.^[3] Protects E.coli against phage T2 infection. When the cdnD-cap2-cap3-cap4 operon is introduced in E.coli there is a more than 10(3) decrease in the efficiency of T2 plaque formation. The operon does not protect against phage T5 and only about 10-fold against T7.^[4]

Publication Abstract from PubMed

Mammalian cyclic GMP-AMP synthase (cGAS) and its homologue dinucleotide cyclase in Vibrio cholerae (VcDncV) produce cyclic dinucleotides (CDNs) that participate in the defense against viral infection. Recently, scores of new cGAS/DncV-like nucleotidyltransferases (CD-NTases) were discovered, which produce various CDNs and cyclic trinucleotides (CTNs) as second messengers. Here, we present the crystal structures of EcCdnD, a CD-NTase from Enterobacter cloacae that produces cyclic AMP-AMP-GMP, in its apo-form and in complex with ATP, ADP and AMPcPP, an ATP analogue. Despite the similar overall architecture, the protein shows significant structural variations from other CD-NTases. Adjacent to the donor substrate, another nucleotide is bound to the acceptor binding site by a non-productive mode. Isothermal titration calorimetry results also suggest the presence of two ATP binding sites. GTP alone does not bind to EcCdnD, which however binds to pppApG, a possible intermediate. The enzyme is active on ATP or a mixture of ATP and GTP, and the best metal cofactor is Mg2+. The conserved residues Asp69 and Asp71 are essential for catalysis, as indicated by the loss of activity in the mutants. Based on structural analysis and comparison with VcDncV and RNA polymerase, a tentative catalytic pathway for the CTN-producing EcCdnD is proposed.

Crystal structure and functional implication of a bacterial cyclic AMP-AMP-GMP synthetase.,Ko TP, Wang YC, Tsai CL, Yang CS, Hou MH, Chen Y Nucleic Acids Res. 2021 Apr 9. pii: 6219115. doi: 10.1093/nar/gkab165. PMID:33836064^[5]

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

References

↑ Lowey B, Whiteley AT, Keszei AFA, Morehouse BR, Mathews IT, Antine SP, Cabrera VJ, Kashin D, Niemann P, Jain M, Schwede F, Mekalanos JJ, Shao S, Lee ASY, Kranzusch PJ. CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection. Cell. 2020 Jun 4. pii: S0092-8674(20)30614-0. doi: 10.1016/j.cell.2020.05.019. PMID:32544385 doi:http://dx.doi.org/10.1016/j.cell.2020.05.019
↑ Millman A, Melamed S, Amitai G, Sorek R. Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems. Nat Microbiol. 2020 Dec;5(12):1608-1615. doi: 10.1038/s41564-020-0777-y. Epub, 2020 Aug 24. PMID:32839535 doi:http://dx.doi.org/10.1038/s41564-020-0777-y
↑ Whiteley AT, Eaglesham JB, de Oliveira Mann CC, Morehouse BR, Lowey B, Nieminen EA, Danilchanka O, King DS, Lee ASY, Mekalanos JJ, Kranzusch PJ. Bacterial cGAS-like enzymes synthesize diverse nucleotide signals. Nature. 2019 Feb 20. pii: 10.1038/s41586-019-0953-5. doi:, 10.1038/s41586-019-0953-5. PMID:30787435 doi:http://dx.doi.org/10.1038/s41586-019-0953-5
↑ Lowey B, Whiteley AT, Keszei AFA, Morehouse BR, Mathews IT, Antine SP, Cabrera VJ, Kashin D, Niemann P, Jain M, Schwede F, Mekalanos JJ, Shao S, Lee ASY, Kranzusch PJ. CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection. Cell. 2020 Jun 4. pii: S0092-8674(20)30614-0. doi: 10.1016/j.cell.2020.05.019. PMID:32544385 doi:http://dx.doi.org/10.1016/j.cell.2020.05.019
↑ Ko TP, Wang YC, Tsai CL, Yang CS, Hou MH, Chen Y. Crystal structure and functional implication of a bacterial cyclic AMP-AMP-GMP synthetase. Nucleic Acids Res. 2021 Apr 9. pii: 6219115. doi: 10.1093/nar/gkab165. PMID:33836064 doi:http://dx.doi.org/10.1093/nar/gkab165

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7d4o"

@@ Line 3: / Line 3: @@
 <StructureSection load='7d4o' size='340' side='right'caption='[[7d4o]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7d4o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"aerobacter_cloacae"_(jordan_1890)_bergey_et_al._1923 "aerobacter cloacae" (jordan 1890) bergey et al. 1923]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D4O FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7d4o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D4O FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.87&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7d48|7d48]], [[7d4j|7d4j]], [[7d4s|7d4s]], [[7d4u|7d4u]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cdnD02, P853_02262 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=550 "Aerobacter cloacae" (Jordan 1890) Bergey et al. 1923])</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=7d4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d4o OCA], [https://pdbe.org/7d4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d4o RCSB], [https://www.ebi.ac.uk/pdbsum/7d4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d4o ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/CDND2_ENTCL CDND2_ENTCL]] CBASS (cyclic oligonucleotide-based antiphage signaling system) provides immunity against bacteriophage. The CD-NTase protein synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signals activate a diverse range of effectors, leading to bacterial cell death and thus abortive phage infection. A type II-C(AAG) CBASS system (PubMed:32839535).<ref>PMID:32544385</ref> <ref>PMID:32839535</ref>   Cyclic trinucleotide synthase that catalyzes the synthesis of 3',3',3'-cyclic AMP-AMP-GMP as the major product, a second messenger for cell signal transduction.<ref>PMID:30787435</ref>   Protects E.coli against phage T2 infection. When the cdnD-cap2-cap3-cap4 operon is introduced in E.coli there is a more than 10(3) decrease in the efficiency of T2 plaque formation. The operon does not protect against phage T5 and only about 10-fold against T7.<ref>PMID:32544385</ref>
+[https://www.uniprot.org/uniprot/CDND2_ENTCL CDND2_ENTCL] CBASS (cyclic oligonucleotide-based antiphage signaling system) provides immunity against bacteriophage. The CD-NTase protein synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signals activate a diverse range of effectors, leading to bacterial cell death and thus abortive phage infection. A type II-C(AAG) CBASS system (PubMed:32839535).<ref>PMID:32544385</ref> <ref>PMID:32839535</ref>   Cyclic trinucleotide synthase that catalyzes the synthesis of 3',3',3'-cyclic AMP-AMP-GMP as the major product, a second messenger for cell signal transduction.<ref>PMID:30787435</ref>   Protects E.coli against phage T2 infection. When the cdnD-cap2-cap3-cap4 operon is introduced in E.coli there is a more than 10(3) decrease in the efficiency of T2 plaque formation. The operon does not protect against phage T5 and only about 10-fold against T7.<ref>PMID:32544385</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Enterobacter cloacae]]
 [[Category: Large Structures]]
-[[Category: Chen, Y]]
+[[Category: Chen Y]]
-[[Category: Hou, M H]]
+[[Category: Hou M-H]]
-[[Category: Ko, T P]]
+[[Category: Ko T-P]]
-[[Category: Tsai, C L]]
+[[Category: Tsai C-L]]
-[[Category: Wang, Y C]]
+[[Category: Wang Y-C]]
-[[Category: Yang, C S]]
+[[Category: Yang C-S]]
-[[Category: Cyclic trinucleotide synthesis nucleotidyl transferase]]
-[[Category: Transferase]]

7d4o

From Proteopedia

Current revision

cyclic trinucleotide synthase CdnD in complex with ATP and ADP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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