附睾蛋白酶抑制剂(EPPIN)是一种雄激素调节的精子结合蛋白(Yenugu S等人。2004)。EPPIN在睾丸和附睾中特别表达(Richardson RT等人2001)。EPPIN涂覆人睾丸和附睾精子的表面作为含有乳酰甲酸酯(LTF)和聚氨酯(CLU)的蛋白质复合物的一部分(Wang Z等人。2007; Paasch U等。2011)。在射精期间,Semenogelin 1(SEMG1)与复合物中的EPPIN结合(Wang Z等人2005; 2007; O'rand Mg等,2009; 2011; Silva EJ等人2012)。已显示复合物,EPPIN,LTF和SEM1衍生肽的组分具有微生物活性。EPPIN表现出对大肠杆菌的剂量和时间依赖性抗菌活性(Yenugu S等人2004)。虽然EPPIN的活性对盐相对不敏感,但它完全损失了EPPIN的CYS残留物的减少和烷基化,表明二硫键的重要性(Yenugu S等人。2004)。此外,EPPIN能够诱导大肠杆菌膜的形态改变,如扫描电子显微镜和测量细菌呼吸电子传输所示(Yenugu S等人2004; McCrudden Mt等,2008)。LTF是一种多官能蛋白,其最为符合其结合铁的能力,最终导致发现其抗菌活性。此外,LTF已经证明了朝着广谱的物种(Legrand D等人)的效力抗病毒,抗真菌和抗遗传活性。 SEMG1-derived peptides were found in the cationic fraction of seminal plasma and showed high levels of antibacterial activity against E. coli and B. megaterium (Bourgeon F et al. 2004; Edstrom AM et al. 2008). The EPPIN protein complex provides antimicrobial activity on the sperm surface. In addition, the binding of SEMG1 to EPPIN during ejaculation inhibits sperm progressive motility, possibly by disturbing the regulation of intracellular pH, resulting in the loss of calcium (O'Rand MG et al, 2009; O'Rand MG & Widgren EE 2012). In parallel, EPPIN inhibits the digestion of SEMG1 by the serine protease prostate specific antigen (PSA), which results in the modulation of semen liquefaction, further prolonging the inhibitory effects of SEMG1 on sperm motility (Wang Z et al. 2005; Wang ZJ et al. 2008; Silva EJ et al. 2013).
EPPIN有两个潜在的蛋白酶抑制结构域:一个乳清酸蛋白(WAP)四型二硫核心(WFDC)结构域和一个Kunitz结构域(Richardson RT et al. 2001;McCrudden et al. 2008)。虽然EPPIN的两个结构域都参与了蛋白的抗菌活性,但只有Kunitz结构域需要选择性蛋白酶抑制(McCrudden MT et al. 2008)。