Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors reveal the molecular basis of high affinity

The atomic-resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors are reported. Each inhibitor contains a benzenesulfonamide prong and a cupric iminodiacetate (IDA-Cu(2+)) prong separated by linkers of different lengths and compositions. The ionized NH(-) group of each benzenesulfonamide coordinates to the active site Zn(2+) ion; the IDA-Cu(2+) prong of the tightest-binding inhibitor, BR30, binds to H64 of CAII and H200 of CAI. This work provides the first evidence verifying the structural basis of nanomolar affinity measured for two-prong inhibitors targeting the carbonic anhydrases.     

Grid Method for Microscale Discontinuous Deformation Measurement

The objective of this paper is to explore both grid method and Digital Image Correlation (DIC) technique for microscale and discontinuous displacement measurements, such as those associated with crack tips. First, the principle of the grid method is revisited. The grid method and DIC technique are then applied to computer generated images to calculate the displacement field around crack tips. Finally, the grid method is applied to actual experimental images of fracture tests which are conducted inside a Scanning Electron Microscope (SEM) chamber. A new technique is developed to generate microscale pattern that is suitable for both grid method and DIC technique. The displacement fields calculated from grid method are compared with those from DIC technique to identify the strengths and weaknesses of each technique for the microscale and discontinuous displacement measurements. It has been determined that grid method can obtain data closer to the discontinuity than DIC; however, DIC produces smoother displacement fields at the far field. Using this new pattern generation technique, both grid method and DIC technique can be applied to the fracture test at the microscale to complement with each other to achieve the best experiment results.