MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Curr Opin Struct Biol. 2013 Dec;23(6):851-8. doi: 10.1016/j.sbi.2013.07.014. Epub 2013 Aug 9.
Rhomboids are intramembrane serine proteases that cleave membrane proteins within the bilayer, and which control a wide variety of biological processes. Recent structures of Escherichia coli rhomboids in complex with mechanism-based inhibitors provide insight into their catalytic mechanism. The inhibitor structures also reveal potential substrate-binding sites within the enzyme and provide a template for modeling substrate binding at the active site. The regulation of rhomboid activity exploits the different membrane compartments in cells to segregate enzyme and substrate. Catalytically inactive rhomboid-like proteins called iRhoms provide another form of regulation, by interacting with rhomboid substrates and preventing their cleavage. Extramembranous domains of rhomboids may play an as yet unexplored role in substrate recognition and regulation.
菱形蛋白酶是一种跨膜丝氨酸蛋白酶，可在双层膜内切割膜蛋白，控制着多种生物过程。最近大肠杆菌菱形蛋白酶与基于机制的抑制剂复合物的结构为其催化机制提供了深入的了解。抑制剂结构还揭示了酶内潜在的底物结合位点，并为在活性位点模拟底物结合提供了模板。菱形蛋白酶活性的调节利用细胞内不同的膜隔室将酶和底物分隔开。催化失活的类菱形蛋白酶称为 iRhoms，通过与菱形蛋白酶底物相互作用并阻止其切割来提供另一种调节形式。菱形蛋白酶的胞外域可能在底物识别和调节中发挥了尚未被探索的作用。
