title: Unnatural amino acid substitution as a probe of the allosteric coupling pathway in a mycobacterial Cu(I) sensor.
abstract: The Cu(I) sensor Mycobacterium tuberculosis CsoR is a founding member of a new metalloregulatory protein family. Here we show that two "atom" substitutions of the Nepsilon2 face of a Cu(I) coordinating histidine-61 allosterically uncouple Cu(I) and DNA binding, with no effect on Cu(I) binding affinity and coordination structure. A model analogous to the allosteric switch mechanism in Staphylococcus aureus CzrA, a zinc sensor protein with a completely different fold, is proposed.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, Indiana 47405-7102, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ma
authors.forename: Darin M
authors.initials: DM
authors.lastname: Cowart
authors.forename: Brian P
authors.initials: BP
authors.lastname: Ward
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Arnold
authors.forename: Richard D
authors.initials: RD
authors.lastname: DiMarchi
authors.forename: Limei
authors.initials: L
authors.lastname: Zhang
authors.forename: Graham N
authors.initials: GN
authors.lastname: George
authors.forename: Robert A
authors.initials: RA
authors.lastname: Scott
authors.forename: David P
authors.initials: DP
authors.lastname: Giedroc
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C517445:CsoR protein, Mycobacterium tuberculosis; D004268:DNA-Binding Proteins; D006639:Histidine; D003300:Copper