1PK0

Crystal Structure of the EF3-CaM complexed with PMEApp


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.302 
  • R-Value Work: 0.264 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection.

Shen, Y.Zhukovskaya, N.L.Zimmer, M.I.Soelaiman, S.Bergson, P.Wang, C.R.Gibbs, C.S.Tang, W.J.

(2004) Proc Natl Acad Sci U S A 101: 3242-3247

  • DOI: https://doi.org/10.1073/pnas.0306552101
  • Primary Citation of Related Structures:  
    1PK0

  • PubMed Abstract: 

    Edema factor (EF), a key virulence factor in anthrax pathogenesis, has calmodulin (CaM)-activated adenylyl cyclase activity. We have found that adefovir dipivoxil, a drug approved to treat chronic infection of hepatitis B virus, effectively inhibits EF-induced cAMP accumulation and changes in cytokine production in mouse primary macrophages. Adefovir diphosphate (PMEApp), the active cellular metabolite of adefovir dipivoxil, inhibits the adenylyl cyclase activity of EF in vitro with high affinity (K(i) = 27 nM). A crystal structure of EF-CaM-PMEApp reveals that the catalytic site of EF forms better van der Waals contacts and more hydrogen bonds with PMEApp than with its endogenous substrate, ATP, providing an explanation for the approximately 10,000-fold higher affinity EF-CaM has for PMEApp versus ATP. Adefovir dipivoxil is a clinically approved drug that can block the action of an anthrax toxin. It can be used to address the role of EF in anthrax pathogenesis.


  • Organizational Affiliation

    Ben-May Institute for Cancer Research, University of Chicago, 924 East 57th Street, Chicago, IL 60637, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Calmodulin-sensitive adenylate cyclase
A, B, C
507Bacillus anthracisMutation(s): 0 
Gene Names: CYA OR PXO1-122
EC: 4.6.1.1
UniProt
Find proteins for P40136 (Bacillus anthracis)
Explore P40136 
Go to UniProtKB:  P40136
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP40136
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Calmodulin
D, E, F
147Homo sapiensMutation(s): 0 
Gene Names: (CALM1 OR CAM1 OR CALM OR CAM)
UniProt & NIH Common Fund Data Resources
Find proteins for P0DP23 (Homo sapiens)
Explore P0DP23 
Go to UniProtKB:  P0DP23
PHAROS:  P0DP23
GTEx:  ENSG00000198668 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DP23
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EMA
Query on EMA

Download Ideal Coordinates CCD File 
H [auth A],
J [auth B],
L [auth C]
(ADENIN-9-YL-ETHOXYMETHYL)-HYDROXYPHOSPHINYL-DIPHOSPHATE
C8 H14 N5 O10 P3
MELHEUHXJKQZNC-UHFFFAOYSA-N
YB
Query on YB

Download Ideal Coordinates CCD File 
G [auth A],
I [auth B],
K [auth C]
YTTERBIUM (III) ION
Yb
AWSFICBXMUKWSK-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
M [auth D]
N [auth D]
O [auth E]
P [auth E]
Q [auth F]
M [auth D],
N [auth D],
O [auth E],
P [auth E],
Q [auth F],
R [auth F]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
EMA PDBBind:  1PK0 Ki: 27 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.30 Å
  • R-Value Free: 0.302 
  • R-Value Work: 0.264 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 116.263α = 90
b = 165.759β = 90
c = 342.409γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-02-10
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2019-11-20
    Changes: Advisory, Derived calculations
  • Version 1.4: 2024-02-14
    Changes: Advisory, Data collection, Database references, Derived calculations