Crystal structure of CntK, the cofactor-independent histidine racemase in staphylopine-mediated metal acquisition of Staphylococcus aureus.

Crystal structure of CntK, the cofactor-independent histidine racemase in staphylopine-mediated metal acquisition of Staphylococcus aureus. Int J Biol Macromol. 2019 May 23;: Authors: Luo S, Ju Y, Zhou J, Gu Q, Xu J, Zhou H Abstract Staphylopine is a newly identified broad-spectrum metallophore for metal acquisition, and it plays important roles in the survival and virulence of Staphylococcus aureus and other pathogens in the metal-scarce environment in hosts. CntK catalyzes the first step of staphylopine synthesis by converting L-histidine to D-histidine to provide an essential building block of staphylopine. Herein, the crystal structures of S. aureus CntK (SaCntK) and its C72S variant are determined at 1.82 and 1.58 Å resolution, respectively. SaCntK forms a homodimer and each subunit contains a two-domain α/β structure. Its overall structure resembles diaminopimelate epimerase, although their sequence identities are lower than 22%. SaCntK is specific for histidine, whereas other proteinogenic amino acids, with the exception of arginine, do not show any binding with SaCntK. Structural modeling suggested that residues Asn16, Glu46, Gln47 and Glu208 are responsible for specific substrate binding, and their substitutions significantly reduced the binding of histidine to SaCntK. Structural modeling suggested SaCntK uses a two-base catalytic mechanism, which has been observed in many cofactor-independent racemases. Our study provi...
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Tags: Int J Biol Macromol Source Type: research