Open AccessStructure of the C‐terminal domain of the arginine repressor protein from Mycobacterium tuberculosis
Author(s) -
Cherney Leonid T.,
Cherney Maia M.,
Garen Craig R.,
Lu George J.,
James Michael N. G.
Publication year - 2008
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s0907444908021513
Subject(s) - random hexamer , arginine , repressor , mycobacterium tuberculosis , chemistry , binding site , stereochemistry , biochemistry , biology , gene , amino acid , gene expression , tuberculosis , medicine , pathology
The Mycobacterium tuberculosis ( Mtb ) gene product encoded by open reading frame Rv1657 is an arginine repressor (ArgR). All genes involved in the l ‐arginine (hereafter arginine) biosynthetic pathway are essential for optimal growth of the Mtb pathogen, thus making Mtb ArgR a potential target for drug design. The C‐terminal domains of arginine repressors (CArgR) participate in oligomerization and arginine binding. Several crystal forms of CArgR from Mtb ( Mtb CArgR) have been obtained. The X‐ray crystal structures of Mtb CArgR were determined at 1.85 Å resolution with bound arginine and at 2.15 Å resolution in the unliganded form. These structures show that six molecules of Mtb CArgR are arranged into a hexamer having approximate 32 point symmetry that is formed from two trimers. The trimers rotate relative to each other by about 11° upon binding arginine. All residues in Mtb CArgR deemed to be important for hexamer formation and for arginine binding have been identified from the experimentally determined structures presented. The hexamer contains six regular sites in which the arginine molecules have one common binding mode and three sites in which the arginine molecules have two overlapping binding modes. The latter sites only bind the ligand at high (200 m M ) arginine concentrations.