A genetically engineered, mutant human alpha-1-proteinase inhibitor is more resistant than the normal inhibitor to oxidative inactivation by chemicals, enzymes, cells, and cigarette smoke.
A genetically engineered, mutant human alpha-1-proteinase inhibitor is more resistant than the normal inhibitor to oxidative inactivation by chemicals, enzymes, cells, and cigarette smoke.
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一种基因工程突变人类 α-1-蛋白酶抑制剂比正常抑制剂更能抵抗化学物质、酶、细胞和香烟烟雾造成的氧化失活。
DOI：
10.1164/arrd.1986.133.3.353
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Rosenberg,S
中科院分区：
文献类型：
--
作者：
Janoff,A;George-Nascimento,C;Rosenberg,S
来自重组酵母的含甲硫氨酸（Met-358）或缬氨酸（Met-瓦尔-358）的α-1-蛋白酶抑制剂（α 1 PI）。将纯蛋白暴露于4种不同氧化系统中的1种：N-氯琥珀酰亚胺（化学氧化）、髓过氧化物酶加过氧化物和卤化物（酶促氧化）、活化的中性粒细胞（细胞氧化）或气相香烟烟雾。然后评估这些处理对两种蛋白质的白细胞弹性蛋白酶抑制功能的影响。经过短暂的曝光，大量的正常抑制剂失活发生，而突变体抑制剂仍然完全活跃。更长时间的暴露导致正常蛋白质的完全失活和突变抑制剂的部分失活。这些结果表明，α 1 PI中的反应中心甲硫氨酰残基比抑制剂中的其他可氧化残基更快地受到氧化剂的影响;然而，Met-358不是α 1 PI中唯一的残基，其修饰可导致该蛋白的弹性蛋白酶抑制能力失活。
Alpha-1-proteinase inhibitors (α1PI) containing methionine (Met-358) or valine (Met➝Val-358) from recombinant yeast. The pure proteins were exposed to 1 of 4 different oxidizing systems: N-chlorosuccinimide (chemical oxidation), myeloperoxidase plus peroxide and halide (enzymatic oxidation), activated neutrophils (cellular oxidation), or gas-phase cigarette smoke. The effect of these treatments on the leukocyte elastase inhibitory function of both proteins was then assessed. After brief exposures, substantial inactivation of the normal inhibitor occurred, whereas the mutant inhibitor remained fully active. More prolonged exposures led to complete inactivation of the normal protein and partial inactivation of the mutant inhibitor. These results suggest that the reactive center methionyl residue inα1PI is more rapidly affected by oxidants than are other oxidizable residues in the inhibitor; however, Met-358 is not the only residue inα1PI whose modification can lead to the inactivation of the elastase inhibitory capacity of this protein.