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H Wade

Publications and source records attributed to H Wade.

10 recordsLinked to original sources
PubMed2001

Toward the de novo design of a catalytically active helix bundle: a substrate-accessible carboxylate-bridged dinuclear metal center.

De novo design of proteins provides an attractive approach to uncover the essential features required for their functions. Previously, we described the design and crystal structure determination of a di-Zn(II) complex of "due-ferri-1" (DF1), a protein patterned after the diiron-dimanganese class of redox-active proteins [Lombardi, A.; Summa, C.; Geremia, S.; Randaccio, L.; Pavone, V.; DeGrado, W. F. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 6298-6305]. The overall structure of DF1, which contains a carboxylate-bridged dinuclear metal site, agrees well with the intended design. However, access to this dimetal site is blocked by a pair of hydrophobic leucine residues (L13 and L13'), which prevent facile entry of metal ions and small molecules. We have now taken the next step in the eventual construction of a catalytically active metalloenzyme by engineering an active site cavity into DF1 through the replacement of these two leucine residues with smaller residues. The crystal structure of the dimanganous form of L13A-DF1 indeed shows a substrate access channel to the dimetal center. In the crystal structure, water molecules and a ligating dimethyl sulfoxide molecule, which forms a monatomic bridge between the metal ions, occupy the cavity. Furthermore, the diferric form of a derivative of L13A-DF1, DF2, is shown to bind azide, acetate, and small aromatic molecules.

Amino Acid Sequence↗
PubMed1997

The structural and functional basis of antibody catalysis.

Ten years have passed since the initial reports that antibodies could be programmed to have enzymatic activity by immunization with a transition-site analog. Much of the research over the last decade has focused on defining the scope and generality of antibody catalysis; however, during the past two years the first few crystal structures of catalytic antibody transition-state analogs have been reported. This review analyzes four such structures of catalytic antibodies that catalyze markedly different reactions, including ester hydrolysis, sulfide oxidation, and a pericyclic rearrangement. Structure-function relations for these catalysts are discussed and compared to the structure and function of natural enzymes, as well as the chemistry that occurs in solution.

Antibodies, Catalytic↗
PubMed1989

A controlled study of luteinizing hormone-releasing hormone agonist (buserelin) for the induction of folliculogenesis before in vitro fertilization.

Treatment with clomiphene citrate and human menopausal gonadotropin (HMG) is often used to induce folliculogenesis before in vitro fertilization, but not all women have an adequate response. It has been hypothesized that abnormally high levels of luteinizing hormone (LH) may contribute to the reduced folliculogenesis. We therefore performed a controlled, open trial in which treatment with buserelin, an agonist of luteinizing hormone-releasing hormone citrate and HMG in 44 consecutive women in whom no oocytes or only one had been produced by standard treatment with clomiphene and HMG. Twenty-nine women received buserelin with HMG, and 15 received clomiphene citrate with HMG. The median number of oocytes per patient recovered from those who received buserelin with HMG was 4 (range, 0 to 19), as compared with 0 (range, 0 to 5) in those who received clomiphene citrate with HMG. The fertilization rates of oocytes recovered from both groups of patients were similar (75.8 percent and 76.5 percent, respectively). Fifty-four percent of patients given buserelin with HMG underwent triple-embryo transfer, as compared with 13 percent of those given clomiphene citrate with HMG. Pregnancy (n = 3) occurred only among the patients receiving buserelin with HMG. In the buserelin-HMG group, significantly fewer oocytes were recovered from patients with occult ovarian failure (infertility and elevated follicular-phase levels of follicle-stimulating hormone, with regular menses) (median, 1; range, 0 to 4) than from those with other causes of infertility (median, 8; range, 0 to 19). Our data suggest that, except in women with occult ovarian failure, buserelin and HMG improve embryologic and clinical outcomes in patients with previously unsatisfactory stimulation of the ovaries for in vitro fertilization.

Administration, Intranasal↗
PubMed1980

The treatment and preoperative diagnosis of differentiated thyroid carcinoma presenting as a clinically solitary nodule.

Some papillary and follicular carcinomas of the thyroid present as solitary nodules with no clinical or radiological evidence of metastases. The elective treatment of such early thyroid carcinomas is discussed, with particular reference to the surgical approach to the clinically solitary nodule. The investigations available for establishing a preoperative diagnosis of the pathology of a solitary nodule are also discussed. A high degree of accuracy is obtainable but absolute certainty, only occasionally. If doubt exists, the safe treatment is excision of the nodule and frozen section.

Adenocarcinoma↗
PubMed1974

Solitary thyroid nodule.

The pathological conditions responsible for a truly solitary thyroid nodule are discussed and a policy of management is outlined for a patient who presents with a clinically solitary nodule. Sophisticated methods of investigation and treatment, while often helpful, are not essential. Scanning is not a highly accurate diagnostic tool, and the solitary nodule can be treated effectively without frozen section or isotopes. The incidence of unsuspected carcinoma in a solitary nodule in a euthyroid patient is high enough to justify exploration in all cases in which the patient is fit for surgery.

Adenoma↗