Payandeh Jian, Fujihashi Masahiro, Gillon Wanda, Pai Emil F
Departmentsof Medical Biophysics, University of Toronto, Division of Cancer Genomics & Proteomics, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada.
J Biol Chem. 2006 Mar 3;281(9):6070-8. doi: 10.1074/jbc.M509377200. Epub 2005 Dec 23.
We report crystal structures of the citrate and sn-glycerol-1-phosphate (G1P) complexes of (S)-3-O-geranylgeranylglyceryl phosphate synthase from Archaeoglobus fulgidus (AfGGGPS) at 1.55 and 2.0 A resolution, respectively. AfGGGPS is an enzyme that performs the committed step in archaeal lipid biosynthesis, and it presents the first triose phosphate isomerase (TIM)-barrel structure with a prenyltransferase function. Our studies provide insight into the catalytic mechanism of AfGGGPS and demonstrate how it selects for the sn-G1P isomer. The replacement of "Helix 3" by a "strand" in AfGGGPS, a novel modification to the canonical TIM-barrel fold, suggests a model of enzyme adaptation that involves a "greasy slide" and a "swinging door." We propose functions for the homologous PcrB proteins, which are conserved in a subset of pathogenic bacteria, as either prenyltransferases or being involved in lipoteichoic acid biosynthesis. Sequence and structural comparisons lead us to postulate an early evolutionary history for AfGGGPS, which may highlight its role in the emergence of Archaea.
我们分别报道了来自嗜热栖热放线菌（AfGGGPS）的（S）-3-O-香叶基香叶基甘油磷酸合酶的柠檬酸盐和sn-甘油-1-磷酸（G1P）复合物的晶体结构，分辨率分别为1.55 Å和2.0 Å。AfGGGPS是一种在古菌脂质生物合成中执行关键步骤的酶，它呈现出具有异戊二烯基转移酶功能的首个磷酸丙糖异构酶（TIM）桶状结构。我们的研究深入了解了AfGGGPS的催化机制，并展示了它如何选择sn-G1P异构体。AfGGGPS中“螺旋3”被“链”取代，这是对经典TIM桶状折叠的一种新颖修饰，提出了一种涉及“滑脂”和“旋转门”的酶适应性模型。我们提出了同源PcrB蛋白的功能，这些蛋白在一部分致病细菌中保守，它们要么作为异戊二烯基转移酶，要么参与脂磷壁酸的生物合成。序列和结构比较使我们推测出AfGGGPS的早期进化历史，这可能突出了它在古菌出现过程中的作用。
