Human α1-Antitrypsin Characterization and N- and C-Terminal Sequences1

Morii, Mitsuyoshi; Okada, Shoji; Koide, Takao; Ikenaka, Tokuji

doi:10.1093/oxfordjournals.jbchem.a131900

Cited by 40 publications

(9 citation statements)

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“…Nucleotides 63 through 1244 code for 394 amino acids, corresponding to the mature a1-antitrypsin protein found in plasma. The first 33 amino acid residues of the amino terminus and 153 amino acid residues from the carboxyl terminus show 96% identity with human a1-antitrypsin (5)(6)(7). This provides good evidence that the cDNA insert in pBaala2 codes for baboon a1-antitrypsin.…”

Section: T C a C A T T A A A G A A G A G T T G A G C T G G A A A A A mentioning

confidence: 65%

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Cloning and sequence of cDNA coding for alpha 1-antitrypsin.

Kurachi¹,

Chandra²,

Degen³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

167

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Recombinant plasmids containing human and baboon cDNA have been screened for a,-antitryJsin, a major serine protease inhibitor present in blood. One plasmid, designated pBaoda2, was found to contain a cDNA insert of 1352 base pairs coding for the baboon inhibitor. It included 45 nucleotides that code for 15 amino acids present in the amino-terminal signal sequence of the protein, 1182 nucleotides that code for 394 amino acids in the mature protein, a stop codon, and a noncoding region of 76 nucleotides. Comparison of the amino acid sequences of baboon a1-antitrypsin, human antithrombin III, and chicken ovalbumin indicated that these three proteins are about 30% homologous. A second plasmid, designated pHalal, was found to contain a human cDNA insert of 306 base pairs. This plasmid coded for 69 amino acids present in the carboxyl-terminal region ofhuman al-antitrypsin. The human and baboon cDNAs and their amino acid sequences are >96% homologous.a1-Antitrypsin [a1-proteinase inhibitor (1)] is an important protease inhibitor present in mammalian blood. Its major physiological function appears to be the inhibition ofneutrophil elastase, a potent protease that hydrolyzes structural proteins (2). It also inhibits many other serine proteases, however, including trypsin, chymotrypsin, collagenase, thrombin, kallikrein, and plasmin (2). The inhibition of the various proteolytic enzymes is due to the formation of a stable, inactive complex containing 1 mol of enzyme and 1 mol of inhibitor. a1-Antitrypsin is a glycoprotein synthesized in the liver. It is composed of a single polypeptide chain (Mr, 50,000) (3) and three carbohydrate chains (4). At present, about 40% of the amino acid sequence has been reported (5-7). This includes regions from the aminoterminal and carboxyl-terminal portions of the molecule.A low level of a1-antitrypsin in the blood is often associated with chronic obstructive pulmonary emphysema and infantile liver cirrhosis (2,8). At present, more than 30 different genetic variants have been identified (1, 9). Several of these are associated with low concentrations of the inhibitor in the blood.The normal plasma level of ar-antitrypsin is about 2 mg/ml. Under most inflammatory conditions, an acute-phase response is initiated and the concentration of a1-antitrypsin is substantially increased (2, 10). In order to study a1-antitrypsin deficiency at the molecular level and examine the mechanism ofthe acute phase response, we have constructed a1-antitrypsin cDNA clones from human and baboon liver mRNAs. In this communication, we report the sequence for a partial human cDNA and a nearly full-length baboon cDNA for a1-antitrypsin and compare the amino acid sequence of this protein with that of antithrombin III and ovalbumin.

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Section: T C a C A T T A A A G A A G A G T T G A G C T G G A A A A A mentioning

confidence: 65%

“…At present, about 40% of the amino acid sequence has been reported (5)(6)(7). This includes regions from the aminoterminal and carboxyl-terminal portions of the molecule.…”

mentioning

confidence: 99%

Cloning and sequence of cDNA coding for alpha 1-antitrypsin.

Kurachi¹,

Chandra²,

Degen³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

167

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“…The result with antithrombin III is not unexpected in view of the considerable homology between arproteinase inhibitor and antithrombin III (Petersen et al, 1979;Carrell et al, 1979;Hunt & Dayhoff, 1980). One major difference between the inhibitors is that arproteinase inhibitor contains no disulfide loops (Morii et al, 1978), and limited proteolysis by proteinase II resulted in release of a 4000-dalton peptide from the molecule. However, antithrombin III contains three disulfide bonds, and all cleavages by proteinase II occurred within disulfide loops at either end of the molecule (Figure 4).…”

Section: Discussionmentioning

confidence: 87%

Identification of the cleavage sites resulting from enzymic inactivation of human antithrombin III by Crotalus adamanteus proteinase II in the presence and absence of heparin

Kress¹,

Catanese²

1981

Biochemistry

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The effect of heparin on the enzymatic inactivation of human antithrombin I11 by Crotalus adamanteus proteinase I1 and the location of the inhibitor bonds cleaved were investigated. Incubation of antithrombin I11 with heparin followed by catalytic amounts of proteinase I1 resulted initially in the conversion of intact inhibitor ( M , 60 000) into an intermediate species ( M , 56 000) which retained inhibitory activity against thrombin. Further proteolysis resulted in the gradual appearance of a third band ( M , 50000) and the corresponding loss of inhibitory activity against thrombin.

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“…An NH2-terminal sequence heterogeneity has also been observed in other serpins. These variants were described to be enzymatic cleavages of the inhibitor unrelated to inhibition of the enzyme (35,36,37).…”

Section: Discussionmentioning

confidence: 99%

Protein C Inhibitor from Human Plasma: Characterization of Native and Cleaved Inhibitor and Demonstration of Inhibitor Complexes with Plasma Kallikrein

Laurell

Stenflo

1989

Thromb Haemost

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SummaryProtein C inhibitor (PCI) was purified from human plasma using immunoaffinity chromatography and heparin Sepharose chromatography, a method that allowed the purification of active and inactive inhibitor. PCI purified from outdated plasma was inactive and either in complex with plasma kallikrein or proteo-lytically degraded. Sequence analysis of cleaved PCI and of complexes between PCI and activated protein C or urokinase identified the previously recognized inhibitor cleavage site Arg354-Ser355. Two additional cleavage sites were observed in the modified inhibitor i.e. Arg357-Leu358 and Arg362-Leu363 which probably represent secondary cleavage of the inhibitor. Furthermore the sequence analysis of the inhibitor, whether purified from fresh or outdated plasma, revealed that it was microheterogeneous in the NH2-terminus as a result of cleavage by a trypsin like enzyme(s).

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Human α1-Antitrypsin Characterization and N- and C-Terminal Sequences1

Cited by 40 publications

References 0 publications

Cloning and sequence of cDNA coding for alpha 1-antitrypsin.

Cloning and sequence of cDNA coding for alpha 1-antitrypsin.

Identification of the cleavage sites resulting from enzymic inactivation of human antithrombin III by Crotalus adamanteus proteinase II in the presence and absence of heparin

Protein C Inhibitor from Human Plasma: Characterization of Native and Cleaved Inhibitor and Demonstration of Inhibitor Complexes with Plasma Kallikrein

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