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P Proctor

Publications and source records attributed to P Proctor.

At least 19 recordsLinked to original sources
PubMed1996

Multiple wavelength anomalous diffraction (MAD) crystal structure of rusticyanin: a highly oxidizing cupredoxin with extreme acid stability.

The X-ray crystal structure of the oxidized form of the extremely stable and highly oxidizing cupredoxin rusticyanin from Thiobacillus ferrooxidans has been determined by the method of multiwavelength anomalous diffraction (MAD) and refined to 1.9 A resolution. Like other cupredoxins, rusticyanin is a copper-containing metalloprotein, which is composed of a core beta-sandwich fold. In rusticyanin the beta-sandwich is composed of a six- and a seven-stranded beta-sheet. Also like other cupredoxins, the copper ion is coordinated by a cluster of four conserved residues (His85, Cys138, His143, Met148) arranged in a distorted tetrahedron. Rusticyanin has a redox potential of 680 mV, roughly twice that of any other cupredoxin, and it is optimally active at pH values < or = 2. By comparison with other cupredoxins, the three-dimensional structure of rusticyanin reveals several possible sources of the chemical differences, including more ordered secondary structure and more intersheet connectivity than other cupredoxins. The acid stability and redox potential of rusticyanin may also be enhanced over other cupredoxins by a more extensive internal hydrogen bonding network and by more extensive hydrophobic interactions surrounding the copper binding site. Finally, reduction in the number of charged residues surrounding the active site may also make a major contribution to acid stability. We propose that the resulting rigid copper binding site, which is constrained by the surrounding hydrophobic environment, structurally and electronically favours Cu(I). We propose that the two extreme chemical properties of rusticyanin are interrelated; the same unique structural features that enhance acid stability also lead to elevated redox potential.

Azurin↗
PubMed1994

Metabolic fate of 14C-camostat mesylate in man, rat and dog after intravenous administration.

1. The metabolic fate of N,N-dimethylcarbamoylmethyl 4-(4-guanidino[14C]benzoyloxy)phenylacetate methanesulphonate (14C-camostat mesylate) was investigated after i.v. administration to man (12-h infusion), and to rat and dog (bolus injection). 2. Renal excretion (mainly in 24 h) accounted for at least 80% dose in all three species, and the only two important metabolites were identified as 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA) and 4-guanidinobenzoic acid (GBA). 3. Parent drug was not detected in human plasma either during or after infusion of 14C-camostat mesylate owing to rapid hydrolysis of the side-chain ester group (t1/2 < 1 min). Steady-state levels of both GBPA and GBA in plasma were apparently attained by the end of the infusion period. Mean terminal half-life, systemic clearance and apparent volume of distribution at steady-state of GBPA in man were 1.0 h, 6.4 ml/min per kg and 0.38 l/kg, respectively, and the corresponding values for GBA were 2.4 h, 4.7 ml/min per kg and 1.01/kg respectively. 4. Radioactivity was rapidly distributed to most tissues after bolus i.v. doses of 14C-camostat mesylate to rats and dogs, with highest levels being associated with the liver and kidney, the two main organs of drug elimination. Concentrations in the pancreas, a possible site for drug action, were generally lower than those in plasma.

Adult↗
PubMed1992

Crystallization and preliminary X-ray crystallographic studies of rusticyanin from Thiobacillus ferrooxidans.

Rusticyanin is a 16.5 kDa type I blue copper protein isolated from Thiobacillus ferrooxidans. This organism can grow on Fe2+ as its sole energy source. Rusticyanin is thought to be a principal component in the iron respiratory electron transport chain of T. ferrooxidans. As a component of the periplasmic space of an acidophilic bacterium, rusticyanin is remarkably stable at acidic pH. It is redox-active down to pH 0.2. Crystals of rusticyanin have been grown from solutions of PEG 8000 by the hanging-drop vapor diffusion method. The crystals are orthorhombic, space group P2(1)2(1)2(1), with unit cell dimensions a = 32.36 A, b = 60.37 A, c = 74.60 A. The crystals diffract to 2.0 A resolution and they are stable in the X-ray beam for at least two days.

Azurin↗
PubMed1991

Crystal parameters and molecular replacement of an anticholera toxin peptide complex.

TE33 is an Fab fragment of a monoclonal antibody raised against a 15-residue long peptide (CTP3), corresponding in sequence to residues 50-64 of the cholera toxin B subunit. Crystals of the complex between TE33 and CTP3 have been grown from 20% (w/v) polyethylene glycol-8000 at pH 4.0. The crystals are orthorhombic, space group P2(1)2(1)2, with unit cell dimensions a = 104.15, b = 110.61, and c = 40.68 A. X-Ray data have been collected to a resolution of 2.3 A. The asymmetric unit contains one molecule of Fab and one molecule of CTP3. The presence of CTP3 has been demonstrated by fluorescence quenching of the dissolved crystal after X-ray data collection. A molecular replacement solution was found based on the coordinates of DB3, an antiprogesterone Fab fragment.

Antibodies, Monoclonal↗
PubMed1989

The mechanical effects of femoral shaft perforation at total hip replacement.

Perforation of the femoral shaft at total hip arthroplasty is a complication which is being reported more frequently. It has been suggested that the presence of bone cement in the perforation decreases the weakening effect of the perforation, but the mechanical basis for this belief is dubious. The anatomy of perforation was studied by cadaver dissection and its mechanical consequences were assessed in two models using Pedilen, a polyurethane foam, and pig femora. It was found that cement in a hole in bone decreased the weakening effect of the hole to tensile stress.

Aged↗
PubMed1977

A superoxide-producing system in the conjunctival mucus thread.

In normal sterile eyes, the conjunctival mucus thread is capable of reducing the vital stain iodonitrotetrazolium (INT). The greatly increased amount of INT reduction in bacterial conjunctivitis has been used as a clinical test for this disorder. We find that native superoxide dismutase, but not the heat inactivated enzyme, inhibits INT reduction by the conjunctival mucus thread in vitro as well as in vivo in sterile rabbit eyes. Furthermore, 3,4-dihydroxybenzoic acid (DHBA), a scavenger of superoxide radical (O2-), inhibits INT reduction by the mucus thread. We conclude that INT reduction by the mucus thread is due to a superoxide radical-producing system similar to that apparently responsible for the tetrazolium-reducing properties of granulocytes and other phagocytes. This oxygen radical-producing system may serve as a defense against infection and possibly as a mediator of the conjunctival inflammatory response.

Animals↗
PubMed1974

Amorphous semiconductor switching in melanins.

Melanins produced synthetically and isolated from biological systems act as an amorphous semiconductor threshold switch. Switching occurs reversibly at potential gradients two to three orders of magnitude lower than reported for inorganic thin films, and comparable to gradients existing in some biological systems. Of a number of other biological materials tested, only cytochrome c acted similarly, but at the high potential gradients reported for thin film amorphous semiconductors.

Cytochrome c Group↗