Unnatural amino acid substitution as a probe of the allosteric coupling pathway in a mycobacterial Cu(I) sensor.
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.
Ma
Zhen
Z
Department of Chemistry, Indiana University, Bloomington, Indiana 47405-7102, USA.
Cowart
Darin M
DM
Ward
Brian P
BP
Arnold
Randy J
RJ
DiMarchi
Richard D
RD
Zhang
Limei
L
George
Graham N
GN
Scott
Robert A
RA
Giedroc
David P
DP
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*
D001426:Bacterial Proteins; C517445:CsoR protein, Mycobacterium tuberculosis; D004268:DNA-Binding Proteins; D006639:Histidine; D003300:Copper