Usman Aminu, Lobb Kevin, Pletschke Brett I, Whiteley Christopher G, Wilhelmi Brendan S
Department of Biochemistry and Microbiology, Rhodes University, P.O. Box 94, Makhanda, (Grahamstown), 6140, South Africa.
Department of Chemistry, Rhodes University, P.O. Box 94, Makhanda, (Grahamstown), 6140, South Africa.
Biochem Biophys Rep. 2021 May 11;26:101013. doi: 10.1016/j.bbrep.2021.101013. eCollection 2021 Jul.
Catechol O-methyltransferase, an enzyme involved in the metabolism of catechol containing compounds, catalyzes the transfer of a methyl group between S-adenosylmethionine and the hydroxyl groups of the catechol. Furthermore it is considered a potential drug target for Parkinson's disease as it metabolizes the drug levodopa. Consequently inhibitors of the enzyme would increase levels of levodopa. In this study, absorption, fluorescence and infrared spectroscopy as well as computational simulation studies investigated human soluble catechol O-methyltransferase interaction with silver nanoparticles. The nanoparticles form a corona with the enzyme and quenches the fluorescence of Trp143. This amino acid maintains the correct structural orientation for the catechol ring during catalysis through a static mechanism supported by a non-fluorescent fluorophore-nanoparticle complex. The enzyme has one binding site for AgNPs in a thermodynamically spontaneous binding driven by electrostatic interactions as confirmed by negative ΔG and ΔH and positive ΔS values. Fourier transform infrared spectroscopy within the amide I region of the enzyme indicated that the interaction causes relaxation of its β-structures, while simulation studies indicated the involvement of six polar amino acids. These findings suggest AgNPs influence the catalytic activity of catechol O-methyltransferase, and therefore have potential in controlling the activity of the enzyme.
儿茶酚-O-甲基转移酶是一种参与含儿茶酚化合物代谢的酶，它催化S-腺苷甲硫氨酸与儿茶酚羟基之间甲基的转移。此外，由于它参与左旋多巴药物的代谢，它被认为是帕金森病的一个潜在药物靶点。因此，该酶的抑制剂会提高左旋多巴的水平。在本研究中，通过吸收光谱、荧光光谱、红外光谱以及计算模拟研究了人可溶性儿茶酚-O-甲基转移酶与银纳米颗粒的相互作用。纳米颗粒与该酶形成一个冠层，并淬灭了Trp143的荧光。在催化过程中，这个氨基酸通过一个由非荧光荧光团-纳米颗粒复合物支持的静态机制维持儿茶酚环的正确结构取向。该酶在由静电相互作用驱动的热力学自发结合过程中有一个银纳米颗粒结合位点，负的ΔG和ΔH值以及正的ΔS值证实了这一点。在该酶的酰胺I区域内进行的傅里叶变换红外光谱表明，这种相互作用导致其β结构松弛，而模拟研究表明有六个极性氨基酸参与其中。这些发现表明银纳米颗粒会影响儿茶酚-O-甲基转移酶的催化活性，因此在控制该酶的活性方面具有潜力。
