FIGURE 3. The membrane-embedded active site of rhomboid protease
a, b, Mutagenesis studies on Drosophila Rhomboid-1 and other rhomboid proteases mapped onto GlpG (viewing angle as in Fig. 2a, b). The GLSG (Gly 199, Ser 201) motif and His 254 are shown in red; His 150 and Asn 154 in orange; Trp 136 and Arg 137 in yellow. Alanine substitution of an arginine in Rhomboid-1 that corresponds to Lys 173 of GlpG (green) also affects activity12: this residue may have a structural function. Alanine substitutions of those residues shown in white do not affect activity12. c, The internal hydrophilic cavity and its front opening. For clarity, the lateral gate (L1) and the cap (L5) have been omitted. The asterisk marks the location of His 254 towards the back of the cavity. The molecular surface is generated by GRASP49. d, A detailed view of the active site and the hydrogen bond network surrounding the catalytic Ser 201 and His 254 (pink). WAT, water molecule (isolated red dots). Only parts of L1, S2, L3, S4, S5 and S6 are shown for clarity. e, Bound water molecules (yellow spheres) within the active site in relation to the conserved GLSG motif and His 254 (red). The boundaries for the hydrophobic region of the membrane are marked by horizontal lines.
生物谷报道：Rhomboid蛋白酶是一种专在膜内发挥作用的蛋白家族，该家族的蛋白可分解其他蛋白的跨膜结构域：很多信号蛋白经过膜内蛋白水解而处于活性状态，而其他一些信号蛋白则转化成溶解性较差的、淀粉质的多肽片段．
近期，美国耶鲁大学医学院的学者，成功确定了Rhomboid蛋白的一个家族成员――存在于大肠杆菌中的GlpG――的晶体结构，该结构显示了它是怎样利用来自膜外的水分子来解离嵌入在膜中的蛋白基质的。这一研究结果发表于最新一期的《Nature》杂志上。此外，催化类似反应的其他Rhomboid家族蛋白也可能有这一机制。其中的一个，即Presenilin，所发生的突变与家族性阿尔茨海默氏症有关。
原文出处:
Nature Volume 444 Number 7116 pp123-242
Crystal structure of a rhomboid family intramembrane protease p179
Yongcheng Wang, Yingjiu Zhang and Ya Ha
Abstract | Full Text | PDF (872K) | Supplementary information
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Nature Volume 444 Number 7116 pp123-242
Structural biology: Enzyme theory holds water p153
Intramembrane proteases have attracted much attention because of their biological and medical value. The first crystal structure of one of these enzymes begins to solve the mystery of how they work.
Matthew Freeman
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