Kumar Suresh
Department of Bioinformatics, School of Biotechnology and Health Sciences, Karunya University, Coimbatore -641114, Tamil Nadu, India;
Bioinformation. 2011;7(7):360-5. doi: 10.6026/97320630007360. Epub 2011 Dec 10.
Cytochromes P450 (CYPs) are a super family of heme-containing enzymes well-known for their monooxgenase reaction. There are 57 CYP isoenzymes found in human which exhibit specific physiological functions. Thirteen members of this super family are classified as "orphan" CYP because of their unknown enzymatic functions. CYP4V2 is found to be a potential drug target for Bietti crystalline corneoretinal dystrophy (BCD). However, three-dimensional structure, the active site topology and substrate binding modes of CYP4V2 remain unclear. In this study, the three-dimensional model of CYP4V2 was constructed using the homology modeling method. Four possible fatty acid substrates namely, caprylic, lauric, myrisitc and palmitic acids were optimized and evaluated for drug likeness using Lipinski's rule of five. Further, these substrates were docked into active sites of CYP4V2 and several key residues responsible for substrate binding were identified. These findings will be helpful for the structure-based drug design and detailed characterization of the biological roles of CYP4V2.
细胞色素P450（CYPs）是一类含血红素的酶超家族，以其单加氧酶反应而闻名。在人类中发现了57种CYP同工酶，它们具有特定的生理功能。该超家族的13个成员因其未知的酶功能而被归类为“孤儿”CYP。CYP4V2被发现是贝蒂氏结晶性角膜视网膜营养不良（BCD）的潜在药物靶点。然而，CYP4V2的三维结构、活性位点拓扑结构和底物结合模式仍不清楚。在本研究中，使用同源建模方法构建了CYP4V2的三维模型。对四种可能的脂肪酸底物，即辛酸、月桂酸、肉豆蔻酸和棕榈酸进行了优化，并使用Lipinski五规则评估了药物相似性。此外，将这些底物对接至CYP4V2的活性位点，并鉴定了几个负责底物结合的关键残基。这些发现将有助于基于结构的药物设计以及对CYP4V2生物学作用的详细表征。
