Crystal Structure of Fad35R from Mycobacterium tuberculosis H37Rv in the Apo-State.

Singh, Appu Kumar and Manjasetty, Babu and Balasubramani, G L and Koul, Sukirte and Kaushik, Abhishek and Ekka, Mary Krishna and Singh, Vijay and Kumaran, Sangaralingam (2015) Crystal Structure of Fad35R from Mycobacterium tuberculosis H37Rv in the Apo-State. PloS one, 10 (5). e0124333. ISSN 1932-6203

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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 α7, 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.

Item Type: Article
Additional Information: 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
Uncontrolled Keywords: Crystal Structure; DNA binding
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 13 Jul 2015 12:52
Last Modified: 14 Jul 2015 05:08

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