Crystallographic studies on carbonic anhydrases from fungal pathogens for structure-assisted drug development
Crystallographic studies on carbonic anhydrases from fungal pathogens for structure-assisted drug development
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用于结构辅助药物开发的真菌病原体碳酸酐酶的晶体学研究
DOI：
10.1002/9780470508169.ch15
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
C. Steegborn
中科院分区：
文献类型：
--
作者：
U.-M. Ohndorf;C. Schlicker;C. Steegborn
碳酸氢酶(CAS，EC 4.2.1.1)是普遍存在的金属酶，催化二氧化碳可逆水合生成碳酸氢盐和质子(图15.1a)。它们参与多种重要的生理功能，如电解质分泌或碳水化合物合成代谢。2 CA存在于生命的各个领域，许多生物含有几种CA亚型。3 CA家族被划分为五个进化上独立的类。A类包括来自细菌、藻类、植物细胞质和脊椎动物的酶。在人类中，15种a-CA亚型(I-XV)参与细胞功能，如呼吸和pH调节。2、4b-cas主要存在于细菌、真菌、藻类和植物叶绿体中，g-cas主要存在于古生菌和一些细菌中。到目前为止，d-cas和最近描述的zcas只在海洋硅藻中已知。1，5虽然不同的CA家族在总体结构上是不相关的(图15.1b)，但CaS的催化中心通常含有一个四面体配位的锌(II)(图15.1a)，除了Thed-CA CDCA1和G-CaS之外，它含有Cd(II)离子，5和g-CaS，它们也以Fe(II)为活性中心离子。6催化离子由三个保守残基配位：三个组氨酸在cas和g-类中，两个半胱氨酸和一个组氨酸在b-类中(图15.1a)。1锌(II)配体的第四个结合部位被水分子占据。在催化循环中，水分子通过质子吸收和形成金属氢氧化物来激活，用于
Carbonic anhydrases (CAs, EC 4.2. 1.1) are ubiquitous metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton (Fig. 15.1 a). 1 They contribute to a wide variety of important physiological functions such as electrolyte secretion or carbohydrate anabolism. 2 CAs are found in all domains of life, with many organisms harboring several CA isoforms. 3 The CA family is divided into five evolutionarily independent classes. 1 The a-class comprises enzymes from bacteria, algae, plant cytosols, and vertebrates. In humans, 15 a-CA isoforms (I–XV) contribute to cellular functions, such as respiration and pH regulation. 2, 4 b-CAs are predominantly found in bacteria, fungi, algae, and plant chloroplasts, and g-CAs are mainly found in archaea and in some bacteria. d-CAs and the recently describedz-CAs are only known in marine diatoms so far. 1, 5Although the different CA families are unrelated in overall structure (Fig. 15.1 b), the catalytic centers of CAs generally contain a tetrahedrally coordinated Zn (II)(Fig. 15.1 a), with the exception of thed-CA CDCA1, which contains a Cd (II) ion instead, 5 andg-CAs, which have also been found with Fe (II) as active site ion. 6The catalytic ion is coordinated by three conserved residues: Three histidines ina-andg-class CAs, and two cysteines and one histidine in the b-class (Fig. 15.1 a). 1 The fourth Zn (II) ligand binding site is occupied by a water molecule. In the catalytic cycle, the water molecule is activated through proton abstraction and formation of a metal hydroxide used for