A structural view of the antibiotic degradation enzyme NDM-1 from a superbug

Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1(NDM-1)are a type of newly discovered antibioticresistant bacteria.The rapid pandemic spread of NDM-1 bacteria worldwide(spreading to India,Pakistan,Europe,America,and Chinese Taiwan)in less than 2 months characterizes these microbes as a potentially major global health problem.The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations.The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics,allowing the bacteria to escape the action of antibiotics.Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues,the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified.Here,we report the threedimensional structure of NDM-1 with two catalytic zinc ions in its active site.Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity.The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases(MBLs)and implicate its role in wide spectrum drug resistance.We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria.Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases.

General closed-form inverse kinematics for arbitrary three-joint subproblems based on the product of exponential model

The inverse kinematics problems of robots are usually decomposed into several Paden–Kahan subproblems based on the product of exponential model. However, the simple combination of subproblems cannot solve all the inverse kinematics problems, and there is no common approach to solve arbitrary three-joint subproblems in an arbitrary postural relationship. The novel algebraic geometric (NAG) methods that obtain the general closed-form inverse kinematics for all types of three-joint subproblems are presented in this paper. The geometric and algebraic constraints are used as the conditions precedent to solve the inverse kinematics of three-joint subproblems. The NAG methods can be applied in the inverse kinematics of three-joint subproblems in an arbitrary postural relationship. The inverse kinematics simulations of all three-joint subproblems are implemented, and simulation results indicating that the inverse solutions are consistent with the given joint angles validate the general closed-form inverse kinematics. Huaque III minimally invasive surgical robot is used as the experimental platform for the simulation, and a master–slave tracking experiment is conducted to verify the NAG methods. The simulation result shows the inverse solutions and six sets given joint angles are consistent. Additionally, the mean and maximum of the master–slave tracking experiment for the closed-form solution are 0.1486 and 0.4777 mm, respectively, while the mean and maximum of the master–slave tracking experiment for the compensation method are 0.3188 and 0.6394 mm, respectively. The experiments results demonstrate that the closed-form solution is superior to the compensation method. The results verify the proposed general closed-form inverse kinematics based on the NAG methods.