Jakobsson P J, Morgenstern R, Mancini J, Ford-Hutchinson A, Persson B
Department of Medical Biochemistry and Biophysics and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 2):S20-4. doi: 10.1164/ajrccm.161.supplement_1.ltta-5.
The members of the MAPEG superfamily have been aligned and found to be distantly related, with a common pattern of hydropathy. Figure 2A shows the multiple sequence alignments of the human members and Figure 2B the corresponding superimposed hydropathy profiles. The alignment in Figure 2A demonstrates a total of six strictly conserved residues. The Arg-51 in LTC4 synthase has been suggested to function as proton donor for the opening of the LTA4 epoxide. This arginine is found in all but the FLAP sequences in accordance with the observation that FLAP has no known enzyme activity. Also the Tyr-93 in LTC4 synthase has been suggested to function as a base for the formation of the thiolate anion of glutathione. This tyrosine is not conserved in MGST1 or MGST1-L1. Table 1 summarizes some other properties of the individual human proteins. They are all of the same size, ranging from 147 to 161 amino acids. Only FLAP differs in that its isoelectric point is more neutral than that of the other, more basic proteins. The genes encoding these proteins all reside on different chromosomes (when known) (Table 1). In addition to the human proteins, MAPEG members have been identified in plants, fungi, and bacteria. It is clearly a challenge to elucidate their role in these different phyla in relation to their defined physiological functions in humans.
MAPEG超家族的成员已进行比对，发现它们有较远的亲缘关系，且具有共同的亲水性模式。图2A展示了人类成员的多序列比对，图2B展示了相应的叠加亲水性图谱。图2A中的比对显示共有六个严格保守的残基。LTC4合酶中的Arg-51被认为作为质子供体参与LTA4环氧化物的开环反应。除了FLAP序列外，在所有序列中都能找到这个精氨酸，这与FLAP没有已知酶活性的观察结果一致。同样，LTC4合酶中的Tyr-93被认为作为碱基参与谷胱甘肽硫醇盐阴离子的形成。这个酪氨酸在MGST1或MGST1-L1中并不保守。表1总结了各个人类蛋白质的一些其他特性。它们大小相同，氨基酸数量在147至161之间。只有FLAP不同，其等电点比其他更碱性的蛋白质更接近中性。编码这些蛋白质的基因都位于不同的染色体上（已知情况）（表1）。除了人类蛋白质外，在植物、真菌和细菌中也鉴定出了MAPEG成员。要阐明它们在这些不同门类中相对于在人类中已明确的生理功能所起的作用，显然是一项挑战。
