7X4P

CD-NTase EfCdnE in complex with intermediate pppUpU


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.188 
  • R-Value Work: 0.149 
  • R-Value Observed: 0.151 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Crystal structure and functional implications of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases.

Yang, C.S.Ko, T.P.Chen, C.J.Hou, M.H.Wang, Y.C.Chen, Y.

(2023) Nat Commun 14: 5078-5078

  • DOI: https://doi.org/10.1038/s41467-023-40787-9
  • Primary Citation of Related Structures:  
    7X4A, 7X4C, 7X4F, 7X4G, 7X4P, 7X4Q, 7X4T, 8HYK

  • PubMed Abstract: 

    Purine-containing nucleotide second messengers regulate diverse cellular activities. Cyclic di-pyrimidines mediate anti-phage functions in bacteria; however, the synthesis mechanism remains elusive. Here, we determine the high-resolution structures of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases (CD-NTases) in clade E (CdnE) in its apo, substrate-, and intermediate-bound states. A conserved (R/Q)xW motif controlling the pyrimidine specificity of donor nucleotide is identified. Mutation of Trp or Arg from the (R/Q)xW motif to Ala rewires its specificity to purine nucleotides, producing mixed purine-pyrimidine cyclic dinucleotides (CDNs). Preferential binding of uracil over cytosine bases explains the product specificity of cyclic di-pyrimidine-synthesizing CdnE to cyclic di-UMP (cUU). Based on the intermediate-bound structures, a synthetic pathway for cUU containing a unique 2'3'-phosphodiester linkage through intermediate pppU[3'-5']pU is deduced. Our results provide a framework for pyrimidine selection and establish the importance of conserved residues at the C-terminal loop for the specificity determination of CD-NTases.


  • Organizational Affiliation

    Genomics BioSci & Tech Co. Ltd., New Taipei, 221, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
EfCdnE307Enterococcus faecalisMutation(s): 0 
EC: 2.7.7
UniProt
Find proteins for P0DX98 (Enterococcus faecalis (strain EnGen0062 / B16457))
Explore P0DX98 
Go to UniProtKB:  P0DX98
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DX98
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.188 
  • R-Value Work: 0.149 
  • R-Value Observed: 0.151 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.332α = 90
b = 56.777β = 97.242
c = 64.78γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data scaling
HKL-2000data reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Academia Sinica (Taiwan)Taiwan--

Revision History  (Full details and data files)

  • Version 1.0: 2023-03-08
    Type: Initial release
  • Version 1.1: 2023-09-13
    Changes: Data collection, Database references
  • Version 1.2: 2023-11-29
    Changes: Refinement description
  • Version 2.0: 2024-05-29
    Changes: Advisory, Atomic model, Author supporting evidence, Data collection, Derived calculations, Non-polymer description