Structure of IDP01169

AtxA protein, a virulence regulator from Bacillus anthracis

Edit deposit information
CSGID target
IDP01169 
PDB Id
4R6I (NCBI MMDB
Authors
J.Osipiuk,L.B.Horton,T.M.Koehler,W.F.Anderson,A.Joachimiak,Center For Structural Genomics Of Infectious Diseases (Csgid) 
Responsible person
Jerzy Osipiuk 
Responsible lab
Argonne National Laboratory 
Deposition Date
Aug 25, 2014 
Release Date
Oct 22, 2014 

Annotation

Description
The Bacillus anthracis virulence regulator AtxA controls transcription of more than a hundred genes including those encoding major virulence factors and capsule biosynthesis. The transcription of atxA gene is affected by temperature, redox potential, growth phase, and the presence of glucose. Additionally, the AtxA activity is regulated by phosphorylation of two specific histidines, H199 and H379. The AtxA crystal structure is multimodular with five distinct domains: two N-terminal DNA-binding domains, two PRDs (phosphoenolpyruvate phosphotransferase system regulation domains) and a C-terminal domain enabling protein dimerization. The H199 histidine is located on the PRD1 domain surface next to DNA-binding domains. The phosphorylation of H199 histidine will presumably change the domains interaction and their relative position in similar way to LicT protein, a PRD-containing anti-terminator protein. This conformational change can facilitate DNA binding. The second histidine undergoing phosphorylation, H379, is located on the PRD2 domain next to the dimerization interface. The His379 phosphorylation impairs AtxA dimers, the protein’s active form, as was deduced from the structure and confirmed by biological experiments. The crystal structure of AtxA is the first reported structure of a PRD-containing virulence regulator. This structure can serve as a model for proteins of this family especially those that link virulence to bacterial metabolism.  
Functional assignment
transcription regulator 

Ligands

Ligand code Name Ligand type
LMT dodecyl-beta-d-maltoside crystallization
175 3,5-dihydro-5-methylidene-4h-imidazol-4-on

Structure information

Unit cell parameters

Space Group
I 2 2 2  
Unit Cell

a=130.46Å, b=135.17Å, c=180.91Å
α=90.00, β=90.00, γ=90.00 
Solvent content
 
Matthews coefficient
 

Refinement

Data for the highest resolution shell is in parentheses.
Resolution range
46.93-2.65Å (2.72-2.65Å)  
Rall(%)
19.9 
Rwork(%)
19.6 (27.3) 
Rfree(%)
25.2 (34.2) 
Num. observed reflections
46330 (3332) 
Num. Rfree reflections
2362 (177) 
Completeness(%)
99.5 (97.7) 

Model parameters

Num Atoms
7475  
Num Waters
72  
Num Hetatoms
321  
Model mean isotropic B factor
81.600Å2  
RMSD bond length
0.011Å  
RMSD bond angle
1.434°  
Filename uploaded
x76b_refmac1.pdb (uploaded on Aug 25, 2014 3:19 PM)  
Inserted
Aug 25, 2014