Singh Dev Bukhsh, Dwivedi Seema
Department of Biotechnology, Institute of Biosciences and Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur, 208024 India ; School of Biotechnology, Gautam Buddha University, Gautam Budh Nagar, 201308 India.
School of Biotechnology, Gautam Buddha University, Gautam Budh Nagar, 201308 India.
J Chem Biol. 2016 Aug 15;9(4):107-120. doi: 10.1007/s12154-016-0155-7. eCollection 2016 Oct.
S-adenosyl-L-homocysteine hydrolase of (PfSAHH) is a potential drug target against malaria, and selective inhibition of PfSAHH is the excellent strategy to prevent the growth of parasite inside the host. Therefore, a comparative analysis of human S-adenosyl-L-homocysteine hydrolase (HsSAHH) and PfSAHH has been performed to explore the structural differences. Structural superimposition of PfSAHH and HsSAHH has generated the RMSD of 0.749 Å over 394 alpha carbon pairs. Residues of PfSAHH from position Tyr152 to Lys193 aligned with insertion/deletion region in HsSAHH, and these extra residues results in an extent of variation in cavity region of PfSAHH. Nicotinamide adenine dinucleotide (NAD) was observed to form hydrogen bonding with Thr201, Thr202, Thr203, Asn235, Val268, Glu287, Asn322, Ile343, Asn391, Lys473, and Tyr477 and also forms hydrophobic interactions with Val268, Ile288, and Thr320 of PfSAHH. In comparison to HsSAHH, Asn322, Lys473, and Tyr477 residues of PfSAHH are unique in interaction with NAD. 2-Fluoroaristeromycin and other analogues of aristeromycin have shown the good binding affinity for both enzymes. Structural differences between PfSAHH and HsSAHH might be employed to design the potential inhibitor of PfSAHH. To find the target enzyme responsible for an anti-malarial effect, molecular docking and interaction analysis of curcumin were performed with 34 drug targets of . Curcumin shows high affinity for binding with HGPRT of PfHGPRT, and an anti-malarial effect of curcumin might be due to binding with PfHGPRT.
疟原虫的S-腺苷-L-高半胱氨酸水解酶（PfSAHH）是抗疟疾的一个潜在药物靶点，选择性抑制PfSAHH是阻止寄生虫在宿主体内生长的极佳策略。因此，已对人S-腺苷-L-高半胱氨酸水解酶（HsSAHH）和PfSAHH进行了比较分析以探究结构差异。PfSAHH和HsSAHH的结构叠加在394个α碳对上产生了0.749 Å的均方根偏差（RMSD）。PfSAHH中从Tyr152到Lys193位置的残基与HsSAHH中的插入/缺失区域对齐，这些额外的残基导致PfSAHH腔区域出现一定程度的变化。观察到烟酰胺腺嘌呤二核苷酸（NAD）与PfSAHH的Thr201、Thr202、Thr203、Asn235、Val268、Glu287、Asn322、Ile343、Asn391、Lys473和Tyr477形成氢键，并且还与PfSAHH的Val268、Ile288和Thr32o形成疏水相互作用。与HsSAHH相比，PfSAHH的Asn322、Lys473和Tyr477残基在与NAD的相互作用方面是独特的。2-氟阿糖腺苷和阿糖腺苷的其他类似物对这两种酶均显示出良好的结合亲和力。PfSAHH和HsSAHH之间的结构差异可用于设计PfSAHH的潜在抑制剂。为了找到负责抗疟作用的靶酶，对姜黄素与疟原虫的34个药物靶点进行了分子对接和相互作用分析。姜黄素显示出与PfHGPRT的次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGPRT）结合的高亲和力，姜黄素的抗疟作用可能归因于与PfHGPRT的结合。
