6JIW

Crystal structure of S. aureus CntK with C72S mutation

6JIW の概要

• エントリーDOI: 10.2210/pdb6jiw/pdb
• 関連するPDBエントリー: 6JIS
• 分子名称: Diaminopimelate epimerase, 1,2-ETHANEDIOL, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: histidine racemase, cobalt and nickel transporter system, isomerase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33209.70

構造登録者

Luo, S.,Ju, Y.,Zhou, H. (登録日: 2019-02-23, 公開日: 2019-10-16, 最終更新日: 2024-10-09)

主引用文献

Luo, S.,Ju, Y.,Zhou, J.,Gu, Q.,Xu, J.,Zhou, H.
Crystal structure of CntK, the cofactor-independent histidine racemase in staphylopine-mediated metal acquisition of Staphylococcus aureus.
Int.J.Biol.Macromol., 135:725-733, 2019

PubMed 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 provides critical insights into the structure and functions of CntK in staphylopine synthesis, which makes it helpful for developing potential antibiotics targeting the staphylopine-mediated metal acquisition process in bacteria.

PubMed: 31129210
DOI: 10.1016/j.ijbiomac.2019.05.169

実験手法

X-RAY DIFFRACTION (1.58 Å)