6E0O

Structure of Elizabethkingia meningoseptica CdnE cyclic dinucleotide synthase with pppA[3'-5']pA

Summary for 6E0O

• Entry DOI: 10.2210/pdb6e0o/pdb
• Descriptor: cGAS/DncV-like nucleotidyltransferase in E. coli homolog, RNA (5'-D(*(ATP))-R(P*A)-3'), MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: cgas, dncv, cyclic dinucleotide, nucleotide second messenger, nucleotidyltransferase, transferase, transferase-rna complex, transferase/rna
• Biological source: Elizabethkingia meningoseptica ATCC 13253 = NBRC 12535; More
• Total number of polymer chains: 3
• Total formula weight: 35770.41

Authors

Eaglesham, J.B.,Whiteley, A.T.,de Oliveira Mann, C.C.,Morehouse, B.R.,Nieminen, E.A.,King, D.S.,Lee, A.S.Y.,Mekalanos, J.J.,Kranzusch, P.J. (deposition date: 2018-07-06, release date: 2019-02-20, Last modification date: 2024-03-13)

Primary citation

Whiteley, A.T.,Eaglesham, J.B.,de Oliveira Mann, C.C.,Morehouse, B.R.,Lowey, B.,Nieminen, E.A.,Danilchanka, O.,King, D.S.,Lee, A.S.Y.,Mekalanos, J.J.,Kranzusch, P.J.
Bacterial cGAS-like enzymes synthesize diverse nucleotide signals.
Nature, 567:194-199, 2019

PubMed Abstract: Cyclic dinucleotides (CDNs) have central roles in bacterial homeostasis and virulence by acting as nucleotide second messengers. Bacterial CDNs also elicit immune responses during infection when they are detected by pattern-recognition receptors in animal cells. Here we perform a systematic biochemical screen for bacterial signalling nucleotides and discover a large family of cGAS/DncV-like nucleotidyltransferases (CD-NTases) that use both purine and pyrimidine nucleotides to synthesize a diverse range of CDNs. A series of crystal structures establish CD-NTases as a structurally conserved family and reveal key contacts in the enzyme active-site lid that direct purine or pyrimidine selection. CD-NTase products are not restricted to CDNs and also include an unexpected class of cyclic trinucleotide compounds. Biochemical and cellular analyses of CD-NTase signalling nucleotides demonstrate that these cyclic di- and trinucleotides activate distinct host receptors and thus may modulate the interaction of both pathogens and commensal microbiota with their animal and plant hosts.

PubMed: 30787435
DOI: 10.1038/s41586-019-0953-5

Experimental method

X-RAY DIFFRACTION (1.25 Å)