据报道,硒结合蛋白1(SELENBP1)在人类中充当甲硫醇氧化酶(MTO),催化甲硫醇转化为过氧化氢,硫化氢和甲醛.这里,我们认为铜离子对这种新型MTO活性至关重要。在大肠杆菌中作为重组蛋白产生的人SELENBP1中推定的铜结合位点的定点诱变导致其酶功能的丧失。另一方面,硒(作为亚硒酸盐)的同名结合对MTO活性没有要求,并且仅适度增加SELENBP1催化的甲硫醇氧化。此外,SEMO-1,最近在线虫C.elegans中发现的SELENBP1直系同源物,还需要铜离子,MTO活动增强或废除,分别,如果蠕虫在氯化铜或铜螯合剂存在下生长。除了甲硫醇,我们从挥发性硫化合物中鉴定了SELENBP1的新型底物,范围从乙硫醇到1-戊硫醇以及2-丙烯-1-硫醇。肠道微生物组衍生的甲硫醇以及食物衍生的挥发性硫化合物(VSCs)造成恶臭,可能导致人类口外口臭,如果代谢不正常。由于SELENBP1在暴露于VSC的组织中特别丰富,如结肠,肝脏,和肺,它似乎有助于铜依赖性VSC降解。
Selenium-binding protein 1 (SELENBP1) was reported to act as a
methanethiol oxidase (MTO) in humans, catalyzing the conversion of
methanethiol to hydrogen peroxide, hydrogen sulfide and formaldehyde. Here, we identify copper ions as essential to this novel MTO activity. Site-directed mutagenesis of putative copper-binding sites in human SELENBP1 produced as recombinant protein in E. coli resulted in loss of its enzymatic function. On the other hand, the eponymous binding of selenium (as selenite) was no requirement for MTO activity and only moderately increased SELENBP1-catalyzed oxidation of
methanethiol. Furthermore, SEMO-1, the SELENBP1 ortholog recently identified in the nematode C. elegans, also requires copper ions, and MTO activity was enhanced or abrogated, respectively, if worms were grown in the presence of cupric chloride or of a Cu chelator. In addition to
methanethiol, we identified novel substrates of SELENBP1 from the group of volatile sulfur compounds, ranging from ethanethiol to 1-pentanethiol as well as 2-propene-1-thiol. Gut microbiome-derived
methanethiol as well as food-derived volatile sulfur compounds (VSCs) account for malodors that may contribute to extraoral halitosis in humans, if not metabolized properly. As SELENBP1 is particularly abundant in tissues exposed to VSCs, such as colon, liver, and lung, it appears to contribute to copper-dependent VSC degradation.