In silico analysis and characterization of GntR family of regulators from Mycobacterium tuberculosis

The genome of Mycobacterium tuberculosis contains a large number of hypothetical and poorly characterized proteins including the proteins belonging to the GntR family. The regulators of this family show a conserved N-terminal DNA-binding domain but have a highly diverse C-terminal domain involved in the effector-binding and/or oligomerization. This heterogeneity has led to a further classification of this family into various subfamilies. The sequence analysis of the M. tuberculosis genome revealed that five genes encode for FadR-like regulators, one gene for HutC-like regulator and one for YtrA-like regulator. This classification was also consistent with specific secondary structural features known to be associated with FadR, HutC and YtrA subfamilies. Out of the five FadR-like regulators three of the regulators were further subclassified into FadR group and two of them into the VanR group. Interestingly Rv3060c, a FadR-like regulator, was shown to have an unusual size which led us to demonstrate it as a product of a gene duplication and fusion event. Thus this study extends the genome annotation of M. tuberculosis and provides important leads for initiating experimental characterization of these proteins, which in turn will enrich our knowledge of their role in cellular physiology. (C) 2006 Elsevier Ltd. All rights reserved.