Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Bioorg Med Chem. 2013 Mar 15;21(6):1570-82. doi: 10.1016/j.bmc.2012.04.044. Epub 2012 Apr 27.
The carbonic anhydrases enzymes (CAs, EC 4.2.1.1) are zinc containing metalloproteins, which efficiently catalyse the reversible conversion of carbon dioxide to bicarbonate and release proton. These enzymes are essentially important for biological system and play several important physiological and patho-physiological functions. There are 16 different alpha-carbonic anhydrase isoforms studied, differing widely in their cellular localization and biophysical properties. The catalytic domains of all CAs possess a conserved tertiary structure fold, with predominately β-strands. We performed an extensive analysis of all 16 mammalian CAs for its structure and function in order to establish a structure-function relationship. CAs have been a potential therapeutic target for many diseases. Sulfonamides are considered as a strong and specific inhibitor of CA, and are being used as diuretics, anti-glaucoma, anti-epileptic, anti-ulcer agents. Currently CA inhibitors are widely used as a drug for the treatment of neurological disorders, anti-glaucoma drugs, anti-cancer, or anti-obesity agents. Here we tried to emphasize how CAs can be used for drug discovery, design and screening. Furthermore, we discussed the role of CA in carbon capture, carbon sensor and metabolon. We hope this review provide many useful information on structure, function, mechanism, and applications of CAs in various discipline.
碳酸酐酶(CAs,EC 4.2.1.1)是含锌的金属蛋白酶,能有效地催化二氧化碳可逆转化为碳酸氢盐并释放质子。这些酶对生物系统至关重要,发挥着多种重要的生理和病理生理功能。目前已研究了 16 种不同的α碳酸酐酶同工酶,它们在细胞定位和生物物理性质上有很大的差异。所有 CAs 的催化结构域都具有保守的三级结构折叠,主要由β-折叠组成。为了建立结构-功能关系,我们对所有 16 种哺乳动物的 CAs 进行了广泛的结构和功能分析。碳酸酐酶一直是许多疾病的潜在治疗靶点。磺胺类药物被认为是 CA 的强特异性抑制剂,被用作利尿剂、抗青光眼、抗癫痫、抗溃疡药物。目前,CA 抑制剂被广泛用作治疗神经紊乱、抗青光眼药物、抗癌或抗肥胖药物的药物。在这里,我们试图强调 CA 如何用于药物发现、设计和筛选。此外,我们还讨论了 CA 在碳捕获、碳传感器和代谢物中的作用。我们希望这篇综述能为 CA 在各个领域的结构、功能、机制和应用提供许多有用的信息。