Four novel mutations in the gene encoding gp91-phox of human NADPH oxidase: consequences for oxidase assembly.
Four novel mutations in the gene encoding gp91-phox of human NADPH oxidase: consequences for oxidase assembly.
复制标题
人类 NADPH 氧化酶 gp91-phox 编码基因的四个新突变：氧化酶组装的后果。
作者：
J. Leusen;C. Meischl;M. Eppink;P. Hilarius;M. de Boer;R. Weening;A. Åhlin;L. Sanders;D. Goldblatt;H. Skopczyńska;E. Bernatowska;J. Palmblad;A. Verhoeven;W. V. van Berkel;D. Roos
The superoxide-forming nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase of human phagocytes comprises membrane-bound and cytosolic proteins, which, upon cell activation, assemble on the plasma membrane to form the active enzyme. Patients with chronic granulomatous disease (CGD) are defective in one of the phagocyte oxidase (phox) components, p47-phox or p67-phox, which reside in the cytosol of resting phagocytes, or gp91-phox or p22-phox, which constitute the membrane-bound cytochrome b(558). In four X-linked CGD patients we have identified novel missense mutations in CYBB, the gene encoding gp91-phox. These mutations were associated with normal amounts of nonfunctional cytochrome b(558) in the patients' neutrophils. In phorbol-myristate-stimulated neutrophils and in a cell-free translocation assay with neutrophil membranes and cytosol, the association of p47-phox and p67-phox with the membrane fraction of the cells with Cys369-->Arg, Gly408-->Glu, and Glu568--> Lys substitutions was strongly disturbed. Only a Thr341-->Lys substitution, residing in a region of gp91-phox involved in flavin adenine dinucleotide (FAD) binding, supported a normal translocation. Thus, the introduction or reversal of charge at residues 369, 408, and 568 in gp91-phox destroys the correct binding of p47-phox and p67-phox to cytochrome b(558). Based on mutagenesis studies of structurally related flavin-dependent oxidoreductases, we propose that the Thr341-->Lys substitution results in impaired hydride transfer from NADPH to FAD. Because we found no electron transfer in solubilized neutrophil plasma membranes from any of the four patients, we conclude that all four amino acid replacements are critical for electron transfer. Apparently, an intimate relation exists between domains of gp91-phox involved in electron transfer and in p47/p67-phox binding. (Blood. 2000;95:666-673)
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影响因子：
15.9
作者：
DINAUER, MC;PIERCE, EA;ORKIN, SH
通讯作者：
ORKIN, SH
影响因子：
56.9
作者：
LETO, TL;LOMAX, KJ;MALECH, HL
通讯作者：
MALECH, HL
影响因子：
2.9
作者：
Medina, M;Martínez-Júlvez, M;Gómez-Moreno, C
通讯作者：
Gómez-Moreno, C
用佛波醇肉豆蔻酸酯乙酸酯刺激后，人中性粒细胞中 NADPH:O2 氧化还原酶的组装和激活。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ambruso,DR;Bolscher,BG;Stokman,PM;Verhoeven,AJ;Roos,D
通讯作者：
Roos,D
一名 69 岁男性患有慢性肉芽肿病。
DOI：
10.1056/nejm199112193252506
发表时间：
1991
期刊：
The New England journal of medicine
影响因子：
--
作者：
Schapiro,BL;Newburger,PE;Klempner,MS;Dinauer,MC
通讯作者：
Dinauer,MC