Department of Plant and Environmental Sciences, Weizmann Institute of Science, 234 Herzl St., Rehovot, 7610001, Israel.
Chembiochem. 2023 Aug 15;24(16):e202300388. doi: 10.1002/cbic.202300388. Epub 2023 Jun 12.
Glycosyltransferases (GTs) are a large and diverse group of enzymes responsible for catalyzing the formation of a glycosidic bond between a donor molecule, usually a monosaccharide, and a wide range of acceptor molecules, thus, playing critical roles in various essential biological processes. Chitin and cellulose synthases are two inverting processive integral membrane GTs, belonging to the type-2 family involved in the biosynthesis of chitin and cellulose, respectively. Herein, we report that bacterial cellulose and chitin synthases share an E-D-D-ED-QRW-TK active site common motif that is spatially co-localized. This motif is conserved among distant bacterial evolutionary species despite their low amino acid sequence and structural similarities between them. This theoretical framework offers a new perspective to the current view that bacterial cellulose and chitin synthases are substrate specific and that chitin and cellulose are organism specific. It lays the ground for future in vivo and in silico experimental assessment of cellulose synthase catalytic promiscuity against uridine diphosphate N-acetylglucosamine and chitin synthase against uridine diphosphate glucose, respectively.
糖基转移酶（GTs）是一大类具有多样性的酶，负责催化供体分子（通常是单糖）与广泛的受体分子之间糖苷键的形成，因此在各种重要的生物过程中起着关键作用。几丁质合酶和纤维素合酶是两种反转的连续整膜 GTs，分别属于涉及几丁质和纤维素生物合成的 2 型家族。在此，我们报告细菌纤维素和几丁质合酶共享一个空间共定位的 E-D-D-ED-QRW-TK 活性位点常见基序。尽管它们之间的氨基酸序列和结构相似性较低，但该基序在不同的细菌进化物种中是保守的。这个理论框架为当前的观点提供了一个新的视角，即细菌纤维素和几丁质合酶是底物特异性的，而几丁质和纤维素是生物体特异性的。它为未来体内和计算机模拟实验评估纤维素合酶对尿苷二磷酸 N-乙酰葡萄糖胺的催化多样性以及几丁质合酶对尿苷二磷酸葡萄糖的催化多样性奠定了基础。
