TY  - JOUR
N1  - This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
ID  - open1635
UR  - http://dx.plos.org/10.1371/journal.pone.0124333
IS  - 5
A1  - Singh, Appu Kumar
A1  - Manjasetty, Babu
A1  - Balasubramani, G L
A1  - Koul, Sukirte
A1  - Kaushik, Abhishek
A1  - Ekka, Mary Krishna
A1  - Singh, Vijay
A1  - Kumaran, Sangaralingam
Y1  - 2015///
N2  - Fad35R from Mycobacterium tuberculosis binds to the promoter site of Fad35 operon and its DNA binding activities are reduced in the presence of tetracycline and palmitoyl-CoA. We resolved the crystal structure of Fad35R using single-wavelength anomalous diffraction method (SAD). Fad35R comprises canonical DNA binding domain (DBD) and ligand binding domain (LBD), but displays several distinct structural features. Two recognition helices of two monomers in the homodimer are separated by ~ 48 Å and two core triangle-shaped ligand binding cavities are well exposed to solvent. Structural comparison with DesT and QacR structures suggests that ligand binding-induced movement of ?7, which adopts a straight conformation in the Fad35R, may be crucial to switch the conformational states between repressive and derepressive forms. Two DBDs are packed asymmetrically, creating an alternative dimer interface which coincides with the possible tetramer interface that connects the two canonical dimers. Quaternary state of alternative dimer mimics a closed-state structure in which two recognition helices are distanced at ~ 35 Å and ligand binding pockets are inaccessible. Results of biophysical studies indicate that Fad35R has the propensity to oligomerize in solution in the presence of tetracycline. We present the first structure of a FadR homologue from mycobacterium and the structure reveals DNA and ligand binding features of Fad35R and also provides a view on alternative quaternary states that mimic open and closed forms of the regulator.
PB  - Public Library of Science
JF  - PloS one
VL  - 10
KW  - Crystal Structure; DNA binding 
SN  - 1932-6203
TI  - Crystal Structure of Fad35R from Mycobacterium tuberculosis H37Rv in the Apo-State.
ER  -