Fujihashi M, Zhang Y W, Higuchi Y, Li X Y, Koyama T, Miki K
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4337-42. doi: 10.1073/pnas.071514398. Epub 2001 Apr 3.
Undecaprenyl diphosphate synthase (UPS) catalyzes the cis-prenyl chain elongation onto trans, trans-farnesyl diphosphate (FPP) to produce undecaprenyl diphosphate (UPP), which is indispensable for the biosynthesis of bacterial cell walls. We report here the crystal structure of UPS as the only three-dimensional structure among cis-prenyl chain elongating enzymes. The structure is classified into a protein fold family and is completely different from the so-called "isoprenoid synthase fold" that is believed to be a common structure for the enzymes relating to isoprenoid biosynthesis. Conserved amino acid residues among cis-prenyl chain elongating enzymes are located around a large hydrophobic cleft in the UPS structure. A structural P-loop motif, which frequently appears in the various kinds of phosphate binding site, is found at the entrance of this cleft. The catalytic site is determined on the basis of these structural features, from which a possible reaction mechanism is proposed.
十一异戊二烯基二磷酸合酶(UPS)催化顺式异戊二烯链在反式,反式-法尼基二磷酸(FPP)上进行延伸,生成十一异戊二烯基二磷酸(UPP),而UPP对于细菌细胞壁的生物合成不可或缺。我们在此报告UPS的晶体结构,它是顺式异戊二烯链延伸酶中唯一的三维结构。该结构被归类于一个蛋白质折叠家族,与被认为是类异戊二烯生物合成相关酶的常见结构的所谓“类异戊二烯合酶折叠”完全不同。顺式异戊二烯链延伸酶中的保守氨基酸残基位于UPS结构中的一个大疏水裂缝周围。在这个裂缝的入口处发现了一个在各种磷酸结合位点中经常出现的结构P环基序。基于这些结构特征确定了催化位点,并据此提出了一种可能的反应机制。