An in silico model of the ferredoxin-dependent nitrate reductase from the cyanobacterium Synechococcus sp. PCC 7942, and information about active sites in related enzymes, had identified Cys148, Met149, Met306, Asp163, and Arg351 as amino acids likely to be involved in either nitrate binding, prosthetic group binding, or catalysis. Site-directed mutagenesis was used to alter each of these residues, and differences in enzyme activity and substrate binding of the purified variants were analyzed. In addition, the effects of these replacements on the assembly and properties of the Mo cofactor and [4Fe-4S] centers were investigated using Mo and Fe determinations, coupled with electron paramagnetic resonance spectroscopy. The C148A, M149A, M306A, D163N, and R351Q variants were all inactive with either the physiological electron donor, reduced ferredoxin, or the nonphysiological electron donor, reduced methyl viologen, as the source of electrons, and all exhibited changes in the properties of the Mo cofactor. Charge-conserving D163E and R351K variants were also inactive, suggesting that specific amino acids are required at these two positions. The implications for the role of these five conserved active-site residues in light of these new results and previous structural, spectroscopic, and mutagenesis studies for related periplasmic nitrate reductases are discussed.
The increase in incidence of M gypseum onychomycosis over the past 2 decades is thought to be due to phylogenetic evolution of the dermatophyte from soil saprophyte to a human parasite. Increasing domestication of mammals is also thought to contribute to increasing incidence. Treatment consists of an extended course of terbinafine or itraconazole.
Eccrine poromas are benign tumors that arise from the eccrine sweat ducts, commonly presenting as solitary lesions. Eccrine poromatosis, the sudden eruption of multiple eccrine poromas, is a rare phenomenon that generally occurs in immunosuppressed patients at any time after receiving treatment for malignancy. We report a case of eccrine poromatosis in a 79-year-old male patient with a previous history of recurrent T-cell lymphoma. Over the course of his disease, he was treated with polychemotherapy, radiation, and a definitive bone marrow transplant. The patient presented to the dermatology clinic 18 years after his initial diagnosis with a new onset of pruritic papules on the neck and chest. Histologic evaluation revealed all lesions to be eccrine poromas. This is the longest reported time interval between initial diagnosis of a primary malignancy and development of eccrine poromatosis. There is no evidence at this time to suggest that appearance of such lesions is indicative of cancer recurrence; therefore, there is no indication for further oncologic evaluation.
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