Alterio Vincenzo, Pan Peiwen, Parkkila Seppo, Buonanno Martina, Supuran Claudiu T, Monti Simona M, De Simone Giuseppina
Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, 80134, Naples, Italy.
Biopolymers. 2014 Jul;101(7):769-78. doi: 10.1002/bip.22456.
Carbonic anhydrase isoform XIV (CA XIV) is the last member of the human (h) CA family discovered so far, being localized in brain, kidneys, colon, small intestine, urinary bladder, liver, and spinal cord. It has recently been described as a possible drug target for treatment of epilepsy, some retinopathies as well as some skin tumors. Human carbonic anhydrase (hCA) XIV is a membrane-associated protein consisting of an N-terminal extracellular domain, a putative transmembrane region, and a small cytoplasmic tail. In this article, we report the expression, purification, and the crystallographic structure of the entire extracellular domain of this enzyme. The analysis of the structure revealed the typical α-CA fold, in which a 10-stranded β-sheet forms the core of the molecule, while the comparison with all the other membrane associated isoforms (hCAs IV, IX, and XII) allowed to identify the diverse oligomeric arrangement and the sequence and structural differences observed in the region 127-136 as the main factors to consider in the design of selective inhibitors for each one of the membrane associated α-CAs.
碳酸酐酶同工酶XIV（CA XIV）是迄今为止发现的人类（h）CA家族的最后一个成员，定位于脑、肾、结肠、小肠、膀胱、肝脏和脊髓。最近它被描述为治疗癫痫、某些视网膜病变以及某些皮肤肿瘤的潜在药物靶点。人碳酸酐酶（hCA）XIV是一种膜相关蛋白，由一个N端细胞外结构域、一个推定的跨膜区域和一个小的细胞质尾巴组成。在本文中，我们报道了该酶整个细胞外结构域的表达、纯化及晶体学结构。结构分析揭示了典型的α-CA折叠，其中一个10股β-折叠形成分子核心，而与所有其他膜相关同工型（hCAs IV、IX和XII）的比较使我们能够确定不同的寡聚排列以及在127-136区域观察到的序列和结构差异，这些是设计针对每种膜相关α-CA的选择性抑制剂时需要考虑的主要因素。
