5XSP

The catalytic domain of GdpP with 5'-pApA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 

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This is version 1.1 of the entry. See complete history


Literature

Structural and biochemical characterization of the catalytic domains of GdpP reveals a unified hydrolysis mechanism for the DHH/DHHA1 phosphodiesterase

Wang, F.He, Q.Su, K.Wei, T.Xu, S.Gu, L.

(2018) Biochem J 475: 191-205

  • DOI: https://doi.org/10.1042/BCJ20170739
  • Primary Citation of Related Structures:  
    5XSI, 5XSN, 5XSP, 5XT3

  • PubMed Abstract: 

    The Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterases (PDEs) that catalyze degradation of cyclic di-adenosine monophosphate (c-di-AMP) could be subdivided into two subfamilies based on the final product [5'-phosphadenylyl-adenosine (5'-pApA) or AMP]. In a previous study, we revealed that Rv2837c, a stand-alone DHH/DHHA1 PDE, employs a 5'-pApA internal flipping mechanism to produce AMPs. However, why the membrane-bound DHH/DHHA1 PDE can only degrade c-di-AMP to 5'-pApA remains obscure. Here, we report the crystal structure of the DHH/DHHA1 domain of GdpP (GdpP-C), and structures in complex with c-di-AMP, cyclic di-guanosine monophosphate (c-di-GMP), and 5'-pApA. Structural analysis reveals that GdpP-C binds nucleotide substrates quite differently from how Rv2837c does in terms of substrate-binding position. Accordingly, the nucleotide-binding site of the DHH/DHHA1 PDEs is organized into three (C, G, and R) subsites. For GdpP-C, in the C and G sites c-di-AMP binds and degrades into 5'-pApA, and its G site determines nucleotide specificity. To further degrade into AMPs, 5'-pApA must slide into the C and R sites for flipping and hydrolysis as in Rv2837c. Subsequent mutagenesis and enzymatic studies of GdpP-C and Rv2837c uncover the complete flipping process and reveal a unified catalytic mechanism for members of both DHH/DHHA1 PDE subfamilies.


  • Organizational Affiliation

    State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphodiesterase acting on cyclic dinucleotides
A, B
343Staphylococcus aureusMutation(s): 0 
Gene Names: cdnDBN1321_430104
UniProt
Find proteins for A0A0U1MUE2 (Staphylococcus aureus)
Explore A0A0U1MUE2 
Go to UniProtKB:  A0A0U1MUE2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0U1MUE2
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.619α = 90
b = 117.263β = 90
c = 127.368γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-01-31
    Type: Initial release
  • Version 1.1: 2023-11-22
    Changes: Data collection, Database references, Derived calculations, Refinement description