Crystalline extracellular nuclease of Staphylococcus aureus.
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Crystallization↗
Biomedical subjects
D C Richardson
Publications and source records attributed to D C Richardson.
Structure and mechanism of copper, zinc superoxide dismutase.
Copper, zinc superoxide dismutase (SOD) catalyses the very rapid two-step dismutation of the toxic superoxide radical (O-2) to molecular oxygen and hydrogen peroxide through the alternate reduction and oxidation of the active-site copper. We report here that after refitting and further refinement of the previous 2 A structure of SOD2, analysis of the new model and its calculated molecular surface shows an extensive surface topography of sequence-conserved residues stabilized by underlying tight packing and H-bonding. There is a single, highly complementary position for O-2 to bind to both the Cu(II) and activity-important Arg 141 with correct geometry; two water molecules form a ghost of the superoxide in this position. The geometry and molecular surface of the active site, together with biochemical data, suggest a specific model for the enzyme mechanism.
Binding Sites↗
Electrostatic recognition between superoxide and copper, zinc superoxide dismutase.
Electrostatic forces have been implicated in a variety of biologically important molecular interactions including drug orientation by DNA, protein folding and assembly, substrate binding and catalysis and macromolecular complementarity with inhibitors, drugs and hormones. To examine enzyme-substrate interactions in copper, zinc superoxide dismutase (SOD), we developed a method for the visualization and analysis of an enzyme's three-dimensional electrostatic vector field that allows the contributions of specific residues to be identified. We report here that the arrangement of electrostatic charges in SOD promotes productive enzyme-substrate interaction through substrate guidance and charge complementarity: sequence-conserved residues create an extensive electrostatic field that directs the negatively charged superoxide (O-2) substrate to the highly positive catalytic binding site at the bottom of the active-site channel. Dissection of the electrostatic potential gradient indicated the relative contributions of individual charged residues: Lys 134 and Glu 131 seem to have important roles in directing the long-range approach of O-2, while Arg 141 has local orienting effects. The reported methods of analysis may have general application for the elucidation of intermolecular recognition processes.
Binding Sites↗
Clinical evaluation of canine acetabular fractures stabilized with an acetabular plate.
A retrospective study of 14 dogs with one or more acetabular fractures stabilized with an acetabular plate was conducted. Twelve of the 14 dogs had additional orthopedic injuries. Follow-up was longer than 6 months. Eleven dogs were evaluated by assessment of radiographs, lameness, mid-thigh circumference, coxofemoral joint range of motion, crepitus, and pain. Varying degrees of osteoarthrosis were noted radiographically at follow-up. Ten of 12 dogs examined had occasional or no clinical lameness. In 10 of 12 dogs, mid-thigh circumference was less on the limb that sustained the acetabular fracture. Nonunion was diagnosed in one plated acetabulum in which two screws had broken. A return to normal or nearly normal function was observed when there were no more than two orthopedic injuries.
Acetabulum↗
Pharmacokinetic disposition of cefazolin in serum and tissue during canine total hip replacement.
Intraoperative cefazolin concentrations were measured in serum, joint capsule, cancellous bone of the acetabulum, and proximal cancellous bone of the femur in 15 dogs undergoing total hip replacement. Cefazolin (22 mg/kg intravenously [IV]) was administered every hour for three doses. The mean peak serum concentrations (+/- SEM) were 387.79 +/- 27.56 micrograms/mL, 521.71 +/- 28.00 micrograms/mL, and 542.20 +/- 30.91 micrograms/mL, respectively. Mean serum concentrations just before administration of doses 2 and 3 were 51.77 +/- 2.39 micrograms/mL, and 64.84 +/- 3.46 micrograms/mL, respectively. The mean cefazolin concentrations in the joint capsule, cancellous bone of the acetabulum, and cancellous bone of the femur were 34.71 +/- 2.50 micrograms/g, 28.70 +/- 7.40 micrograms/g, and 36.20 +/- 3.80 micrograms/g, respectively. The minimum inhibitory concentration of cefazolin for 90% of the common contaminants (MIC90) in this clinic is less than or equal to 2 micrograms/mL or per gram of tissue. Serum concentrations never fell below 15 times the MIC90 (lowest trough, 35.93 micrograms/mL), and the lowest tissue concentration (6.57 micrograms/mL in cancellous bone from the acetabulum) was still more than 3 times the MIC90. The mean tissue concentration was 15 times the MIC90.
Acetabulum↗
Subsidence of an uncemented canine femoral stem.
Factors contributing to subsidence were analyzed by radiographic evaluation and mechanical testing of 36 canine cadaver femora during and after insertion of an uncemented porous-coated femoral stem and by radiographic evaluation of 35 canine total hip arthroplasties. Mean percentage of canal fill in immediate postoperative radiographs, and percentage of canal fill at midimplant and distal implant locations, were accurate predictors of subsidence. Force required to implant the femoral stem was strongly correlated with force required for implant subsidence. Femoral morphology and percentage of canal fill at the middle and distal sites were accurate predictors of subsidence. Implants in femora with a stovepipe morphology (canal flare index less than or equal to 1.8) were six times more likely to subside than implants in femora that had a normal appearance (canal flare index 1.8 to 2.5), and 72 times more likely to subside than implants in champagne-fluted femora (canal flare index greater than or equal to 2.5). Femora with more than 85% mean, middle, or distal canal fill were less likely to subside.
Animals↗
Lateral patellar luxation in miniature horses.
Bilateral luxation of the patella in four Miniature Horses was corrected by a lateral release incision and medial imbrication of the parapatellar fascia to the tendon of the sartorius muscle. Before surgery, the four horses had a grade 3 to 4 lateral patellar luxation bilaterally and had difficulty walking. Trochlear ridge hypoplasia was evident on radiographs in each horse. Follow-up information varied from 11 months to 4 years after surgery. Three horses had no patellar luxation or lameness. The other horse had a normal right stifle, but patellar luxation (grade 3) had recurred on the left.
Animals↗
Biomechanical evaluation of a toggle pin technique for management of coxofemoral luxation.
Toggle pin stabilization is an accepted technique for the management of coxofemoral (CF) luxation in dogs. The purpose of this study was to determine, in vitro, the respective contributions of several aspects of toggle pin repair to the overall stability of fixation. Factors evaluated were the manner and frequency with which toggle pins oriented on insertion, effect of orientation on toggle pin strength, effect of suture type on ligament prosthesis strength and load sustained by the fixation, and comparison of repair using a modified toggle design to that of capsulorrhaphy. When placed in cadavers using standard technique, conventional toggle pins were found to orient significantly more frequently in one of two possible positions. Mechanical testing of fixations performed in experimentally luxated cadaver hips demonstrated a high (12/20) incidence of toggle pin failure using the conventional implant in the most common orientation. When tested alone, toggle pins were weakest mechanically in this orientation. Rotating the implant 180 degrees increased mean load to failure by 249%. There was no significant difference in load sustained by conventional toggle fixations using No. 2 braided polyester versus 50 lb test monofilament nylon as the suture ligament prosthesis. However, the higher stiffness of the polyester suture may be more favorable for use in this application. Fixation using a toggle rod designed to allow evaluation of construct stability when failure of the toggle is eliminated resulted in an increase in maximum load sustained before luxation (47% of the intact control hips). This load was not significantly different than the resistance to luxation afforded by capsulorrhaphy. This study suggests that when implanting conventional toggle pins, consideration should be given to ensuring placement in the strongest orientation.
Animals↗