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P Edwards

Publications and source records attributed to P Edwards.

At least 37 records · Page 2Linked to original sources

The crystal structure of beta-ketoacyl-acyl carrier protein synthase II from Synechocystis sp. at 1.54 A resolution and its relationship to other condensing enzymes.

Condensing enzymes, catalyzing the formation of carbon-carbon bonds in several biosynthetic pathways, have lately been recognized as potential drug targets against cancer and tuberculosis, as crucial for combinatorial biosynthesis of antibiotics and related compounds, and as determinants of plant oil composition. beta-Ketoacyl-ACP synthases (KAS) are the condensing enzymes present in the fatty acid biosynthesis pathway and are able to elongate an acyl chain bound to either co-enzyme A (CoA) or acyl carrier protein (ACP) with a two-carbon unit derived from malonyl-ACP. Several isoforms of KAS with different substrate specificity are present in most species. We have determined the crystal structure of KAS II from Synechocystis sp. PCC 6803 to 1.54 A resolution giving a detailed description of the active site geometry. In order to analyze the structure-function relationships in this class of enzymes in more detail, we have compared all presently known three-dimensional structures of condensing enzymes from different pathways. The comparison reveals that these enzymes can be divided into three structural and functional classes. This classification can be related to variations in the catalytic mechanism and the set of residues in the catalytic site, e.g. due to differences in the nature of the second substrate providing the two-carbon elongation unit. The variation in the acyl-carrier (ACP or CoA) specificity might also be connected to this classification and residues involved in ACP binding in structure class 2 can be suggested based on the comparison. Finally, the two subunits in the dimer contribute differently to formation of the substrate binding-pocket in the three structural classes.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

Overexpression of 3-ketoacyl-acyl-carrier protein synthase IIIs in plants reduces the rate of lipid synthesis.

A cDNA coding for 3-ketoacyl-acyl-carrier protein (ACP) synthase III (KAS III) from spinach (Spinacia oleracea; So KAS III) was used to isolate two closely related KAS III clones (Ch KAS III-1 and Ch KAS III-2) from Cuphea hookeriana. Both Ch KAS IIIs are expressed constitutively in all tissues examined. An increase in the levels of 16:0 was observed in tobacco (Nicotiana tabacum, WT-SR) leaves overexpressing So KAS III when under the control of the cauliflower mosaic virus-35S promoter and in Arabidopsis and rapeseed (Brassica napus) seeds overexpressing either of the Ch KAS IIIs driven by napin. These data indicate that this enzyme has a universal role in fatty acid biosynthesis, irrespective of the plant species from which it is derived or the tissue in which it is expressed. The transgenic rapeseed seeds also contained lower levels of oil as compared with the wild-type levels. In addition, the rate of lipid synthesis in transgenic rapeseed seeds was notably slower than that of the wild-type seeds. The results of the measurements of the levels of the acyl-ACP intermediates as well as any changes in levels of other fatty acid synthase enzymes suggest that malonyl-ACP, the carbon donor utilized by all the 3- ketoacyl-ACP synthases, is limiting in the transgenic plants. This further suggests that malonyl-coenzyme A is a potential limiting factor impacting the final oil content as well as further extension of 16:0.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

Oesophagogastric cancer and surgical subspecialisation: how much work?

The aim of this study was to assess the volume of work generated by one consultant (out of a surgical unit of seven) managing all the upper gastrointestinal malignancy in a district general hospital serving a population of 480,000. A 3-year period was prospectively audited and the volume of out-patient and in-patient workload assessed with particular reference to resource management and levels of surgical staffing. Oesophagogastric cancer accounted for a mean of 61 new cases per year, representing 5.3% of new patient referrals. Assuming that a complex major operation for an oesophagogastric cancer equates to four intermediate equivalent values (IEVs), then this translated to a mean operative workload of 186 IEVs per year, representing 16.7% of the total elective operative workload of 1140 IEVs per year. Thus, all the oesophagogastric cancer was managed by a single firm as a speciality in a district general hospital over this 3-year period, though a relatively small proportion of new patients with oesophagogastric cancer translated into a significantly greater burden on the resources of consultant manpower and operating theatre time.

Esophageal Neoplasms↗

Contamination of the surgical field.

Is there sufficient evidence to suggest that the wearing of face masks is imperative during surgical procedures for maximum patient protection? Or is it just another ritual that needs to be re-examined in the light of today's emphasis on evidence-based medicine. Should we be re-educating theatre staff that the wearing face masks is more for their own protection than for that of the patient? To help us towards some conclusions, Peggy Edwards presents the results of her review of the literature on the face mask debate.

Air Microbiology↗