Department of Chemistry, Indian Institute of Technology, New Delhi, India.
Department of Chemistry, Indian Institute of Technology, New Delhi, India.
Int J Biol Macromol. 2018 Feb;107(Pt B):1915-1921. doi: 10.1016/j.ijbiomac.2017.10.053. Epub 2017 Oct 13.
Present work reports the inhibition of Bacillus cereus EMB20 β-lactamase by a deep eutectic solvent, maline in an uncompetitive manner. Far-UV CD and intrinsic fluorescence spectroscopy revealed a disrupted secondary as well as tertiary structure as a function of maline concentration. The effect of individual components of maline on β-lactamase inhibition showed that malonic acid was mainly responsible for inhibiting the β-lactamase. Structural and docking studies found that malonic acid led to major perturbations in the secondary and tertiary structure of the enzyme while H-bonding with the active site residues. Further the antibacterial and cytotoxic studies also confirmed the potential of maline as a potent growth inhibitor of β-lactamase producing B. cereus EMB20.
本工作报道了一种深共晶溶剂——丙二酸，以非竞争方式抑制蜡样芽胞杆菌 EMB20 β-内酰胺酶。远紫外圆二色性（CD）和内源荧光光谱研究表明，随着丙二酸浓度的增加，酶的二级和三级结构被破坏。丙二酸对β-内酰胺酶抑制作用的各个组分的影响表明，丙二酸主要负责抑制β-内酰胺酶。结构和对接研究发现，丙二酸导致酶的二级和三级结构发生重大变化，同时与活性位点残基形成氢键。此外，抗菌和细胞毒性研究也证实了丙二酸作为一种潜在的、能强烈抑制产β-内酰胺酶蜡样芽胞杆菌 EMB20 生长的物质。
