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P Loewen

Publications and source records attributed to P Loewen.

6 recordsLinked to original sources
PubMed1998

E. coli HPII catalase interaction with high spin ligands: formate and fluoride as active site probes.

E. coli catalase (HPII) wild type and mutant enzymes (heme dcis-containing) were examined (i) to study the role of a distal haem cavity residue, asparagine-201, in high spin ligand binding and (ii) to compare the differences in this binding between heme d and protoheme enzymes such as that from beef liver (BLC). High spin fluoride complexes were formed by all three HPII catalases examined, wild type (201 asn) and 201gln and 201asp mutants, but with a lower fluoride affinity than that of BLC. The binding of fluoride was pH-dependent, indicating that a proton is bound as well as a fluoride anion. HPII 201glu and 201 asp mutants showed lower affinities for fluoride than did wild type, unlike their reactions with cyanide which are essentially independent of the nature of residue 201. The equilibria and rates of fluoride and formate binding to BLC were reexamined. The rates of reaction with formate were similar to those reported previously. Dissociation rates for fluoride-catalase are higher than for formate suggesting that the latter may be bound differently. High spin complexes between formate and all three HPII forms showed a substantially higher affinity than that of BLC for HPII wild type and progressively lower affinities for the two mutants. As with fluoride the reactions were pH-dependent, indicating that a proton is bound together with the formate anion (or that undissociated formic acid is the ligand). The known structures of the heme groups and heme pockets involved are discussed. Formate may be bound by secondary H-bounds within the heme pocket in both heme dcis and protoheme enzymes. The nature of the heme pocket and the heme access channel may be more important than the chemical nature of the prosthetic group in controlling both high spin ligand interactions and reactions with the substrate hydrogen peroxide.

Bacterial Proteins↗
PubMed1998

Upper extremity performance and self-care skill changes in children with spastic cerebral palsy following selective posterior rhizotomy.

Changes in upper extremity and self-care performance following selective posterior rhizotomy (SPR) are reported frequently, but rarely quantified. In this study, 36 children with spastic cerebral palsy were assessed preoperatively and 1 year following SPR using the Quality of Upper Extremity Skills Test (QUEST). Twenty-six children were assessed at similar intervals using the Functional Independence Measure for Children (WeeFIM) as a measure of self-care performance. Wilcoxon matched-pair signed-rank tests were used to compare the QUEST total scores and the WeeFIM motor, cognitive, and total scores before and after SPR. One year after SPR, the total QUEST scores were significantly better (median improvement = 3.2%, p < 0.0001), as were the WeeFIM motor (median improvement = 9.5, p < 0. 0001), cognitive (median improvement = 1.0, p < 0.008), and total (median improvement = 11.0, p < 0.0001) scores. The results indicate quantifiable improvements in upper extremity function, and motor and cognitive self-care skills in children 1 year after SPR.

Activities of Daily Living↗
PubMed1998

The efficacy and safety of combination warfarin and ASA therapy: a systematic review of the literature and update of guidelines.

The English-language literature was systematically reviewed to clarify the role of combination antithrombotic therapy with warfarin and acetylsalicylic acid (ASA) versus monotherapy with either agent, including data from several recently published trials. Sixteen published studies with evaluable efficacy and/or safety data were identified. For patients with prosthetic heart valves at high risk of thromboembolism, combined warfarin and ASA therapy may be beneficial compared with warfarin alone. Combination therapy may also be used for primary prevention in patients at high risk for ischemic heart disease, although the expected benefits are small. Evidence does not support the use of combined antithrombotic therapy in patients with established ischemic heart disease, ischemic stroke, coronary artery bypass grafts or atrial fibrillation. Combination therapy is associated with an increased risk of minor and major bleeding. The highest dose of ASA that can be recommended in combination with warfarin is 100 mg daily.

Anticoagulants↗
PubMed1997

Activity, peroxide compound formation, and heme d synthesis in Escherichia coli HPII catalase.

Wild-type Escherichia coli HPII catalase (heme d containing) has 15% the activity of beef liver enzyme per heme. The rate constant for compound I formation with H2O2 is 1.3 x 10(6) M(-1) s(-1). HPII compound I reacts with H2O2 to form O2 with a rate constant of 1.8 x 10(6) M(-1) s(-1). Forty percent of HPII hemes are in the compound I state during turnover. Compound I is reduced by ethanol and formate at rates of 5 and 13 M(-1) s(-1) (pH 7.0), respectively. Incubation of HPII compound I with ferrocyanide and ascorbate does not form a compound II species. Mutation of His128 to alanine or asparagine gives inactive protoheme proteins. Mutation of Asn201 gives partially active heme d forms. Asn201Ala has 24%, Asn201Asp 10%, and Asn201Gln 0.4% of wild-type activity. Asn201His contains protoheme when isolated and converts this via protoheme compound I to a heme d species. Both distal heme cavity residues His128 and Asn201 are implicated in catalytic activity, compound I formation, and in situ heme d biosynthesis. HPII Asn201, like the corresponding residue in protoheme catalases, may promote H+ transfer to His128 imidazole, facilitating (i) peroxide anion binding to heme and (ii) stabilization of a transition state for heterolytic cleavage of the O-O bond.

Animals↗
PubMed1996

Probing the structure of catalase HPII of Escherichia coli--a review.

Escherichia coli produces two catalases or hydroperoxidases, HPI and HPII. HPI is a bifunctional catalase-peroxidase active as a tetramer of identical 80049-Da subunits encoded by katG. The expression of katG is controlled at the basal level by sigma s (KatF), and its induction by H2O2 is regulated by OxyR. HPII is a monofunctional catalase active as a tetramer of identical 84118-Da subunits encoded by katE. The induction of katE expression in the stationary phase is controlled by sigma s. The core of HPII is similar in sequence to other catalases including the conservation of several residues that have been implicated as playing a catalytic role, His128, Asn201, Ser167 and Tyr415. These residues have served as targets for site-directed mutagenesis in a study that has demonstrated their role in the catalytic mechanism of HPII. In addition, the two Cys residues in HPII have been targeted in a similar study revealing that they do not have a catalytic role, but that Cys438 is blocked by a novel modification. Despite many structural similarities to bovine liver catalase, the heme component of HPII has proved to be quite different. The presence of a cis heme d was determined spectrally and chromatographically, and the inability of certain mutants to generate the modified heme revealed that it was HPII itself that was catalysing the oxidation of heme b to heme d. The recent solution of the crystal structure of HPII and mass spectrometry have revealed that the heme d bound to HPII is a spirolactone structure with a cis orientation of the oxygens on the proximal side of the heme. This has created the problem of explaining how the oxidation of the heme can occur on the opposite side of the heme ring, remote from the catalytic residues.

Bacterial Proteins↗