The crystal structure of a class II fructose-1,6-bisphosphate aldolase shows a novel binuclear metal-binding active site embedded in a familiar fold

BACKGROUND: [corrected] Aldolases catalyze a variety of condensation and cleavage reactions, with exquisite control on the stereochemistry. These enzymes, therefore, are attractive catalysts for synthetic chemistry. There are two classes of aldolase: class I aldolases utilize Schiff base formation with an active-site lysine whilst class II enzymes require a divalent metal ion, in particular zinc. Fructose-1,6-bisphosphate aldolase (FBP-aldolase) is used in gluconeogenesis and glycolysis; the enzyme controls the condensation of dihydroxyacetone phosphate with glyceraldehyde-3-phosphate to yield fructose-1,6-bisphosphate. Structures are available for class I FBP-aldolases but there is a paucity of detail on the class II enzymes. Characterization is sought to enable a dissection of structure/activity relationships which may assist the construction of designed aldolases for use as biocatalysts in synthetic chemistry. RESULTS: The structure of the dimeric class II FBP-aldolase from Escherichia coli has been determined using data to 2.5 A resolution. The asymmetric unit is one subunit which presents a familiar fold, the (alpha/beta)8 barrel. The active centre, at the C-terminal end of the barrel, contains a novel bimetallic-binding site with two metal ions 6.2 A apart. One ion, the identity of which is not certain, is buried and may play a structural or activating role. The other metal ion is zinc and is positioned at the surface of the barrel to participate in catalysis. CONCLUSIONS: Comparison of the structure with a class II fuculose aldolase suggests that these enzymes may share a common mechanism. Nevertheless, the class II enzymes should be subdivided into two categories on consideration of subunit size and fold, quaternary structure and metal-ion binding sites.     

Are maternal diabetes and preeclampsia independent simulators of fetal erythropoietin production?

To determine if diabetes and preeclampsia are independent stimulators of erythropoietin, distinct from hypoxia, we measured umbilical cord plasma erythropoietin in 239 deliveries from 24 to 40 weeks of gestation. Mean plasma erythropoietin levels were not different between normal, diabetic, and preeclamptic women when all deliveries were analyzed. When infants with suspected intrauterine hypoxia were excluded, the mean erythropoietin level was considerably lower within all three groups but there was no difference among the groups. In suspected hypoxia, the mean fetal erythropoietin was elevated, but there was no difference between control, diabetic, or preeclamptic pregnancies. These results provide further support that hypoxia remains the only known stimulator of erythropoietin production in the fetus.     

Inhibition of white blood cell adhesion at reperfusion decreases tissue damage in postischemic striated muscle

By correlating data obtained from environmental indicators and health indicators over a five-year period, a system for measuring the effects of air pollution on health has been established and tested. Rises in air pollution levels do appear to be accompanied by increases in the relevant health problems.     

A 1957 outbreak of Legionnaires' disease associated with a meat packing plant

Retrospective study shows that a 1957 outbreak of pneumonia in Austin, Minnesota, was Legionnaires' disease. Between June 7 and August 9, 1957, 78 persons were hospitalized with acute respiratory disease of unknown cause. Most had fever, headache, cough, and pneumonitis; two died. Ages ranged from 14-83 years; half of the patients were aged 55 years or older. Eighty-seven per cent were men. There were no secondary cases. Forty-six (59%) of the 78 patients were employees at a local meat packing plant, in distinction to the area's total working population (32%). Serosurvey of 15 of the 1957 outbreak cases and 30 controls matched for age, sex, and either occupation or residence was carried out in 1979. Antibody titers were determined for Legionella pneumophila serogroups 1-4 by means of indirect immunofluorescence. Twelve (80%) of the 15 cases and 13 (43%) of the 30 controls had antibody titers of 1:64 or greater to one or more of the L. pneumophila serogroups. Significant differences in L. pneumophila antibody titers (prevalence and level) were found between cases and control groups matched for residence (serogroups 1-3) or occupation (serogroups 2 and 3). Only three of 20 Austin residents with pneumonia diagnosed between 1978 and 1980 had L. pneumophila antibody titers of 1:128 or greater (p less than 0.001), in comparison to cases. These serologic data and the 1957 clinical and epidemiologic observations support the contention that this is the earliest documented outbreak of Legionnaires' disease.     

Formation of the nicotinic acetylcholine receptor binding sites

Nicotinic acetylcholine receptors (AChRs) are activated by ACh binding to two sites located on different alpha subunits. The two alpha subunits, alpha gamma and alpha delta, are distinguished by their interface with gamma and delta subunits. We have characterized the formation of the ACh binding sites and found, contrary to the current model, that the sites form at different times and in a set order. The first site forms on alpha gamma subunits during the process of subunit assembly. Our data are consistent with the appearance of this site on alpha beta gamma delta subunit tetramers soon after the site for the competitive antagonist alpha-bungarotoxin has formed and delta subunits have assembled with alpha beta gamma trimers. The second site is located on alpha delta subunits and forms after AChR subunits have assembled into alpha2 beta gamma delta pentamers. By determining the order in which the ACh binding sites form, we have also identified the sites in which the delta and second alpha subunits associate during subunit assembly.     

Treatment of Goodpasture syndrome with cyclophosphamide, prednisone and plasma exchange transfusions

Repeated plasm exchanges were performed in a 44-year-old man with Goodpasture syndrome, also treated with cyclophosphamide and prednisone. Improvement was observed within 3 weeks of starting the protocol, and by the 76th week, endogenous creatinine clearance had increased from 30 to 56 ml/min/1.73 M2 and serum albumin from 2.7 to 3.7 g/dl. Prior treatment with immunosuppressive drugs had not significantly influenced circulating antibody levels. But sustained suppression of antibody was achieved after the plasma exchanges were begun, suggesting that physical removal of circulating antibody combined with antiproliferative drug treatment may be a useful way to control undesirable humoral immune responses.     

Predictive validity of the interview.

This paper describes the use of the interview technique as a valid and reliable instrument for predicting job placement and vocational success. The interviews of 144 blind adults were objectively and quantitatively scored, making full use of all responses elicited by the S. The results indicated that job success and vocational placement are significantly related to a number of variables tapped by the interview, such as perception of blindness, learned ways of dealing with tension, interpersonal interaction, and employment potential. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute renal failure: a study of the course and prognosis of 104 patients and of the role of furosemide

Cortisone, aldosterone or nialamide was administered to adrenalectomized or sham-operated rats for 7 days, and methamphetamine was injected 24 hrs after the last injection of these compounds. Stereotyped head movement and licking activity were scored 5 min, 30 min and 60 min after methamphetamine injection and, in parallel brain methamphetamine levels in similarly treated rats were measured 5 min, 30 min and 60 min after the methamphetamine injection. Adrenalectomy depressed stereotyped head movements but enhanced the brain amphetamine accumulation. Nialamide but not the hormones further increased the amphetamine accumulation in adrenalectomized rats. No drugs had any effect on the amphetamine-induced head movement suppressed by adrenalectomy.