70 kilodalton heat shock protein (bacterial Hsp70 homolog) (DnaK)

DnaK is the major bacterial homolog of the heat shock protein 70 (Hsp70) family. It functions as a molecular chaperone, facilitating the folding and refolding of proteins, preventing aggregation under stress, and maintaining overall proteome stability[1][3][4][5][6]. DnaK cycles between ATP- and ADP-bound states, working in concert with co-chaperones DnaJ (J-domain protein) and GrpE (nucleotide exchange factor) to bind client proteins, stimulate ATP hydrolysis, and promote proper folding[2][3][5]. Highly conserved across bacteria, DnaK is essential under heat and chemical stress and is required for the growth and virulence of many pathogenic species[3][5]. Recent research highlights DnaK as a promising antibacterial target, as small-molecule and peptide-based inhibitors can disrupt its activity, potentially sensitizing bacteria to conventional antibiotics or inhibiting the evolution of resistance[3]. DnaK's role in proteostasis, stress response, and pathogenesis make it a central therapeutic target and a key player in bacterial cell biology[1][3][5].

Other names

DnaKHsp70 (specifically refers to bacterial Hsp70, but "Hsp70" alone is more commonly used for eukaryotic family members)

Inhibition of ATPase activity (blocks chaperone function required for protein folding); Disruption of substrate binding (interferes with interaction between DnaK and misfolded/unfolded proteins); Synergism with antibiotics (inhibition of DnaK can potentiate effects of existing antibiotics); Disruption of interaction with co-chaperones DnaJ and GrpE (essential for chaperone cycle)