Tsukamoto K, Kikura R, Ohno R, Sawai T
Division of Microbial Chemistry, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
FEBS Lett. 1990 May 21;264(2):211-4. doi: 10.1016/0014-5793(90)80250-m.
On the assumption that Asp-217 of a Citrobacter freundii cephalosporinase forms a salt-bridge with the conserved Lys-67, Asp-217 was changed to glutamic acid, threonine or lysine. The mutant enzymes retained about the same level of activity as that of the wild-type enzyme, and the participation of Asp-217 in the salt-bridge was ruled out. However, the mutations resulted in an increase in hydrolytic activity toward oxyimino-cephalosporins such as cefuroxime, cefmenoxime and ceftazidime, suggesting a possible mechanism of the bacterial resistance to the novel beta-lactams by a single mutation in cephalosporinases.
假定弗氏柠檬酸杆菌头孢菌素酶的天冬氨酸-217与保守的赖氨酸-67形成盐桥，将天冬氨酸-217分别突变为谷氨酸、苏氨酸或赖氨酸。突变酶保留了与野生型酶大致相同水平的活性，排除了天冬氨酸-217参与盐桥形成的可能性。然而，这些突变导致对肟基头孢菌素如头孢呋辛、头孢甲肟和头孢他啶的水解活性增加，这表明头孢菌素酶中的单个突变可能是细菌对新型β-内酰胺耐药的一种机制。
