1985
DOI: 10.1038/313149a0
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Abstract: The primary function of alpha 1-antitrypsin (alpha 1-AT), an antiprotease produced by the liver, is the inhibition of neutrophil elastase, a protease capable of hydrolysing most connective tissue components. The importance of alpha 1-AT is demonstrated by the high incidence of early-onset emphysema in individuals with hereditary alpha 1-AT deficiency (Type PiZZ), in whom serum levels of alpha 1-AT are 10-20% of normal. Oxidants in tobacco smoke can inactivate alpha 1-AT in vitro, and studies have shown that al… Show more

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Cited by 130 publications
(60 citation statements)
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“…Site-specific mutants in which methionine 358 was changed to valine were shown to be relatively resistant to oxidative inactivation by several laboratories (39,40). These reports have understandably led to the impression that methionine 351 is not important in the oxidative inactivation of "1-AT, but the issue had not been directly investigated.…”
Section: Discussionmentioning
confidence: 99%
“…Site-specific mutants in which methionine 358 was changed to valine were shown to be relatively resistant to oxidative inactivation by several laboratories (39,40). These reports have understandably led to the impression that methionine 351 is not important in the oxidative inactivation of "1-AT, but the issue had not been directly investigated.…”
Section: Discussionmentioning
confidence: 99%
“…To facilitate further analysis, al-PI with an Arg in place of the natural Met358 ( Fig. 1 B) has been chosen as the starting point for further amino acid exchanges, since this variant is a good inhibitor of a-thrombin, a proteinase easily measurable in an in vitro inhibitory assay [14,15]. The dcsign of [Met351 -+ Glu, Met358 + Arg]al-PI was based on a suggestion that strand incorporation might occur sequentially starting at Thr345 [231.…”
Section: Resultsmentioning
confidence: 99%
“…Oligonucleotide directed mutagenesis of the cDNA coding for [Met358 -+ Arg]al-PI with a deletion of its five N-termind amino acids was performed as previously described [15,161. Expression of [Thr345 4 Arg, Met358 + ArgJal-Pi, [Met351 --$ Glu, Met358 -+Arg]a,-PI and [Met358 +Arg]al-PI was carried out in Escherichia coli (strain TGE 901) from plasmids pTG 7952, pTG 7955 and pTG 1943, respectively, under the control of the leftward promoter of phage 1 .…”
Section: Production Of A-pi Variantsmentioning
confidence: 99%
“…Recombinant forms of α1AT have not been effective when administered intravenously as those raised in yeast are non-glycosylated with a resultant very short plasma half life while those produced from transgenic animals had different glycosylation to plasma purified α1AT also leading to alterations in half life. [74][75][76]. Animal studies evaluating intravenous infusion of SLPI showed an unacceptably high level of proteinuria [77].…”
Section: Augmentation With Purified Plasma α1atmentioning
confidence: 99%