Yuan Yanqiu, Barrett Dianah, Zhang Yi, Kahne Daniel, Sliz Piotr, Walker Suzanne
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5348-53. doi: 10.1073/pnas.0701160104. Epub 2007 Mar 8.
Peptidoglycan is an essential polymer that forms a protective shell around bacterial cell membranes. Peptidoglycan biosynthesis is the target of many clinically used antibiotics, including the beta-lactams, imipenems, cephalosporins, and glycopeptides. Resistance to these and other antibiotics has prompted interest in an atomic-level understanding of the enzymes that make peptidoglycan. Representative structures have been reported for most of the enzymes in the pathway. Until now, however, there have been no structures of any peptidoglycan glycosyltransferases (also known as transglycosylases), which catalyze formation of the carbohydrate chains of peptidoglycan from disaccharide subunits on the bacterial cell surface. We report here the 2.1-A crystal structure of the peptidoglycan glycosyltransferase (PGT) domain of Aquifex aeolicus PBP1A. The structure has a different fold from all other glycosyltransferase structures reported to date, but it bears some resemblance to lambda-lysozyme, an enzyme that degrades the carbohydrate chains of peptidoglycan. An analysis of the structure, combined with biochemical information showing that these enzymes are processive, suggests a model for glycan chain polymerization.
肽聚糖是一种重要的聚合物，它在细菌细胞膜周围形成一层保护壳。肽聚糖生物合成是许多临床使用抗生素的作用靶点，包括β-内酰胺类、亚胺培南、头孢菌素和糖肽类。对这些及其他抗生素产生耐药性，促使人们想要在原子水平上了解合成肽聚糖的酶。该合成途径中大多数酶的代表性结构已被报道。然而，迄今为止，尚未有任何肽聚糖糖基转移酶（也称为转糖基酶）的结构报道，这类酶催化细菌细胞表面二糖亚基形成肽聚糖的碳水化合物链。我们在此报告嗜热栖热菌PBP1A的肽聚糖糖基转移酶（PGT）结构域的2.1埃晶体结构。该结构与迄今报道的所有其他糖基转移酶结构具有不同的折叠方式，但与λ-溶菌酶有一些相似之处，λ-溶菌酶是一种降解肽聚糖碳水化合物链的酶。对该结构的分析，结合显示这些酶具有连续性的生化信息，提示了一种聚糖链聚合模型。
