| Inhibition of fumarase activity using Zn modified CQDs |
| کد مقاله : 1278-ICOC |
| نویسندگان |
|
حمیدرضا کلهر، آمنه نواصر * دانشگاه صنعتی شریف |
| چکیده مقاله |
| Enzymes are versatile biological catalysts capable of performing both highly specific and promiscuous reactions [1]; Therefore, regulating their activity is essential for controlling metabolic pathways and developing targeted therapeutic strategies. Fumarase (Figure 1) is a key citric acid cycle enzyme that interconverts fumarate and L-malate (Figure 2) and is important for energy metabolism and redox balance [2]. Several organic small molecules were initially tested as potential regulators but showed no measurable effect on fumarase activity . To explore metal-based enzyme regulation, the inhibitory effects of zinc ions and zinc-modified carbon quantum dots (Zn-CQDs) on recombinant Saccharomyces cerevisiae fumarase were examined. Enzyme kinetics were measured in both reaction directions, with Zn2+ ions or Zn-CQDs added as potential inhibitors. Characterization of Zn-CQDs showed typical carbon quantum dot features—UV-vis peaks at ~240 and ~340 nm, excitation-dependent photoluminescence and functional groups detected by FT-IR (including Zn–O), an amorphous structure by XRD, and ~5 nm spherical particles by TEM, with 22.6 wt% Zn incorporation. Kinetics studies were performed. Both Zn2+ and Zn-CQDs were acted as competitive inhibitors, increasing Km without affecting Vmax, and showing stronger inhibition in the reverse reaction . Zn-CQDs displayed markedly higher potency due to improved solubility and more effective Zn2+ delivery to the enzyme surface. Docking studies supported these findings, showing Zn2+ binding within the active site through interactions with residues Asn56, Asn339, and Glu340.Overall, Zn-CQDs provided a more effective and tunable strategy for fumarase inhibition than free Zn2+, highlighting their potential for targeted metabolic regulation and therapeutic applications. |
| کلیدواژه ها |
| Fumarase, Enzyme regulation, Carbon quantum dot, Zinc ions. |
| وضعیت: پذیرفته شده |