{ "labelLang" : "hun", "responseDate" : "2024-03-29 05:51", "content" : { "otype" : "JournalArticle", "mtid" : 31414281, "status" : "APPROVED", "published" : true, "comment" : "Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, United States \n Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United States \n Canadian Blood Services, Centre for Innovation, Hamilton, ON, Canada \n Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada \n Export Date: 25 August 2020 \n CODEN: PRCIE \n Correspondence Address: Sheffield, W.P.; Canadian Blood Services, Centre for InnovationCanada; email: sheffiel@mcmaster.ca \n Chemicals/CAS: activated protein C; alpha 1 antitrypsin, 9041-92-3; thrombin, 9002-04-4, 869858-13-9 \n Funding details: Canadian Blood Services, CBS \n Funding details: National Institute of Standards and Technology, NIST \n Funding details: Health Canada \n Funding text 1: B.M.S. is an International Associate of the National Institute of Standards and Technology (NIST). NIST notes that certain commercial materials are identified in this article to specify an experimental procedure as completely as possible. In no case does the identification of particular materials imply a recommendation or endorsement by NIST, nor does it imply that the particular materials are necessarily the best available for the purpose. The opinions expressed in this article are the authors' own and do not necessarily represent the views of NIST. W.P.S. is Associate Director, Research, Centre for Innovation, Canadian Blood Services. Since the Centre for Innovation receives funds from Health Canada, a department of the federal government of Canada, this article must contain the statement, ?The views expressed herein do not necessarily represent the views of the federal government.?", "unhandledTickets" : 0, "deleted" : false, "lastRefresh" : "2022-04-29T07:58:35.517+0000", "lastModified" : "2021-06-23T08:51:58.223+0000", "created" : "2020-08-25T13:45:05.979+0000", "creator" : { "otype" : "Author", "mtid" : 10015069, "link" : "/api/author/10015069", "label" : "Dobó József (biokémia és immunológia)", "familyName" : "Dobó", "givenName" : "József", "published" : true, "oldId" : 10015069, "snippet" : true }, "lastDuplumSearch" : "2023-01-25T13:55:10.234+0000", "core" : false, "citation" : true, "publicationPending" : false, "type" : { "otype" : "PublicationType", "mtid" : 24, "link" : "/api/publicationtype/24", "label" : "Folyóiratcikk", "code" : 24, "otypeName" : "JournalArticle", "listPosition" : 1, "published" : 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Techniques used to engineer α1-AT include targeted mutagenesis, protein fusions, phage display, glycoengineering, and consensus protein design. The goals of engineering have also been diverse, ranging from understanding serpin structure–function relationships, to the design of more potent or more specific proteinase inhibitors with potential therapeutic relevance. 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serpins (1989) Biochemistry, 28, pp. 8951-8966 ;\n Law, R.H., Zhang, Q., McGowan, S., An overview of the serpin superfamily (2006) Genome Biol, 7, p. 216 ;\n Rawlings, N.D., Barrett, A.J., Thomas, P.D., Huang, X., Bateman, A., Finn, R.D., The MEROPS database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database (2018) Nucleic Acids Res, 46, pp. D624-D632 ;\n Silverman, G.A., Whisstock, J.C., Bottomley, S.P., Serpins flex their muscle: I. putting the clamps on proteolysis in diverse biological systems (2010) J Biol Chem, 285, pp. 24299-24305 ;\n Heit, C., Jackson, B.C., McAndrews, M., Update of the human and mouse SERPIN gene superfamily (2013) Hum Genomics, 7, p. 22 ;\n Baumann, H., Gauldie, J., The acute phase response (1994) Immunol Today, 15, pp. 74-80 ;\n Crystal, R.G., The alpha 1-antitrypsin gene and its deficiency states (1989) Trends Genet, 5, pp. 411-417 ;\n Perlmutter, D.H., Alpha-1-antitrypsin deficiency: Importance of proteasomal and autophagic degradative pathways in disposal of liver disease-associated protein aggregates (2011) Annu Rev Med, 62, pp. 333-345 ;\n Landrum, M.J., Lee, J.M., Benson, M., ClinVar: Improving access to variant interpretations and supporting evidence (2018) Nucleic Acids Res, 46, pp. D1062-D1067 ;\n Salahuddin, P., Genetic variants of alpha1-antitrypsin (2010) Curr Protein Pept Sci, 11, pp. 101-117 ;\n Hazari, Y.M., Bashir, A., Habib, M., Alpha-1-antitrypsin deficiency: Genetic variations, clinical manifestations and therapeutic interventions (2017) Mutat Res, 773, pp. 14-25 ;\n de Serres, F.J., Blanco, I., Fernandez-Bustillo, E., PI S and PI Z alpha-1 antitrypsin deficiency worldwide. A review of existing genetic epidemiological data (2007) Monaldi Arch Chest Dis, 67, pp. 184-208 ;\n Gooptu, B., Dickens, J.A., Lomas, D.A., The molecular and cellular pathology of alpha(1)-antitrypsin deficiency (2014) Trends Mol Med, 20, pp. 116-127 ;\n Carrell, R.W., What we owe to alpha(1)-antitrypsin and to Carl-Bertil Laurell (2004) COPD, 1, pp. 71-84 ;\n Long, G.L., Chandra, T., Woo, S.L., Davie, E.W., Kurachi, K., Complete sequence of the cDNA for human alpha 1-antitrypsin and the gene for the S variant (1984) Biochemistry, 23, pp. 4828-4837 ;\n Loebermann, H., Tokuoka, R., Deisenhofer, J., Huber, R., Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function (1984) J Mol Biol, 177, pp. 531-557 ;\n Bollen, A., Herzog, A., Cravador, A., Cloning and expression in Escherichia coli of full-length complementary DNA coding for human alpha 1-antitrypsin (1983) DNA, 2, pp. 255-264 ;\n Cabezon, T., De Wilde, M., Herion, P., Loriau, R., Bollen, A., Expression of human alpha 1-antitrypsin cDNA in the yeast Saccharomyces cerevisiae (1984) Proc Natl Acad Sci U S A, 81, pp. 6594-6598 ;\n Karnaukhova, E., Ophir, Y., Golding, B., Recombinant human alpha-1 proteinase inhibitor: Towards therapeutic use (2006) Amino Acids, 30, pp. 317-332 ;\n Krishnan, B., Hedstrom, L., Hebert, D.N., Gierasch, L.M., Gershenson, A., Expression and purification of active recombinant human Alpha-1 antitrypsin (AAT) from Escherichia coli (2017) Methods Mol Biol, 1639, pp. 195-209 ;\n Tamer, I.M., Chisti, Y., Production and recovery of recombinant protease inhibitor α1-antitrypsin (2001) Enzyme Microb Technol, 29, pp. 611-620 ;\n Karnaukhova, E., Recent advances in the research and development of alpha-1 proteinase inhibitor for therapeutic use (2012) Lung diseases - selected state of the art reviews, pp. 83-104. , Irusen M, editor., London, United Kingdom, InTech, p ;\n Janciauskiene, S., Welte, T., Well-known and less well-known functions of alpha-1 antitrypsin. Its role in chronic obstructive pulmonary disease and other disease developments (2016) Ann Am Thorac Soc, 13, pp. S280-S288 ;\n Wanner, A., Alpha-1 antitrypsin as a therapeutic agent for conditions not associated with alpha-1 antitrypsin deficiency (2016) Alpha-1 antitrypsin: Role in health and disease, pp. 141-155. , Wanner A, Sandhaus RA, editors., Cham, Springer International Publishing, p ;\n Duranton, J., Bieth, J.G., Inhibition of proteinase 3 by [alpha]1-antitrypsin in vitro predicts very fast inhibition in vivo (2003) Am J Respir Cell Mol Biol, 29, pp. 57-61 ;\n Duranton, J., Adam, C., Bieth, J.G., Kinetic mechanism of the inhibition of cathepsin G by alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor (1998) Biochemistry, 37, pp. 11239-11245 ;\n Lockett, A.D., Van Demark, M., Gu, Y., Effect of cigarette smoke exposure and structural modifications on the alpha-1 antitrypsin interaction with caspases (2012) Mol Med, 18, pp. 445-454 ;\n Shapiro, L., Pott, G.B., Ralston, A.H., Alpha-1-antitrypsin inhibits human immunodeficiency virus type 1 (2001) FASEB J, 15, pp. 115-122 ;\n Kaner, Z., Ochayon, D.E., Shahaf, G., Acute phase protein alpha1-antitrypsin reduces the bacterial burden in mice by selective modulation of innate cell responses (2015) J Infect Dis, 211, pp. 1489-1498 ;\n Ehlers, M.R., Immune-modulating effects of alpha-1 antitrypsin (2014) Biol Chem, 395, pp. 1187-1193 ;\n Pott, G.B., Chan, E.D., Dinarello, C.A., Shapiro, L., Alpha-1-antitrypsin is an endogenous inhibitor of proinflammatory cytokine production in whole blood (2009) J Leukoc Biol, 85, pp. 886-895 ;\n Janciauskiene, S.M., Nita, I.M., Stevens, T., Alpha1-antitrypsin, old dog, new tricks. Alpha1-antitrypsin exerts in vitro anti-inflammatory activity in human monocytes by elevating cAMP (2007) J Biol Chem, 282, pp. 8573-8582 ;\n Bergin, D.A., Reeves, E.P., Hurley, K., The circulating proteinase inhibitor alpha-1 antitrypsin regulates neutrophil degranulation and autoimmunity (2014) Sci Transl Med, 6 ;\n Bergin, D.A., Reeves, E.P., Meleady, P., Alpha-1 antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8 (2010) J Clin Invest, 120, pp. 4236-4250 ;\n Gordon, S.M., McKenzie, B., Kemeh, G., Rosuvastatin alters the proteome of high density lipoproteins: Generation of alpha-1-antitrypsin enriched particles with anti-inflammatory properties (2015) Mol Cell Proteomics, 14, pp. 3247-3257 ;\n Rosenberg, S., Barr, P.J., Najarian, R.C., Hallewell, R.A., Synthesis in yeast of a functional oxidation-resistant mutant of human alpha-antitrypsin (1984) Nature, 312, pp. 77-80 ;\n Elliott, P.R., Abrahams, J.P., Lomas, D.A., Wild-type alpha 1-antitrypsin is in the canonical inhibitory conformation (1998) J Mol Biol, 275, pp. 419-425 ;\n Patston, P.A., Gettins, P.G., Schapira, M., Serpins are suicide substrates: Implications for the regulation of proteolytic pathways (1994) Semin Thromb Hemost, 20, pp. 410-416 ;\n Huntington, J.A., Serpin structure, function and dysfunction (2011) J Thromb Haemost, 9, pp. 26-34 ;\n Huntington, J.A., Thrombin inhibition by the serpins (2013) J Thromb Haemost, 11, pp. 254-264 ;\n Sifers, R.N., Intracellular processing of alpha1-antitrypsin (2010) Proc Am Thorac Soc, 7, pp. 376-380 ;\n Casolaro, M.A., Fells, G., Wewers, M., Augmentation of lung antineutrophil elastase capacity with recombinant human alpha-1-antitrypsin (1987) J Appl Physiol, 63, pp. 2015-2023 ;\n Hopkins, P.C., Carrell, R.W., Stone, S.R., Effects of mutations in the hinge region of serpins (1993) Biochemistry, 32, pp. 7650-7657 ;\n Avron, A., Reeve, F.H., Lickorish, J.M., Carrell, R.W., Effect of alanine insertion (P'5) on the reactive centre of alpha 1-antitrypsin (1991) FEBS Lett, 280, pp. 41-43 ;\n Djie, M.Z., Stone, S.R., Le Bonniec, B.F., Intrinsic specificity of the reactive site loop of alpha1-antitrypsin, alpha1-antichymotrypsin, antithrombin III, and protease nexin I (1997) J Biol Chem, 272, pp. 16268-16273 ;\n Luo, L.Y., Jiang, W., Inhibition profiles of human tissue kallikreins by serine protease inhibitors (2006) Biol Chem, 387, pp. 813-816 ;\n Beatty, K., Bieth, J., Travis, J., Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin (1980) J Biol Chem, 255, pp. 3931-3934 ;\n Felber, L.M., Kundig, C., Borgono, C.A., Mutant recombinant serpins as highly specific inhibitors of human kallikrein 14 (2006) FEBS J, 273, pp. 2505-2514 ;\n Ellis, V., Scully, M., MacGregor, I., Kakkar, V., Inhibition of human factor Xa by various plasma protease inhibitors (1982) Biochim Biophys Acta, 701, pp. 24-31 ;\n Scott, C.F., Schapira, M., James, H.L., Cohen, A.B., Colman, R.W., Inactivation of factor XIa by plasma protease inhibitors: Predominant role of alpha 1-protease inhibitor and protective effect of high molecular weight kininogen (1982) J Clin Invest, 69, pp. 844-852 ;\n Mahrus, S., Kisiel, W., Craik, C.S., Granzyme M is a regulatory protease that inactivates proteinase inhibitor 9, an endogenous inhibitor of granzyme B (2004) J Biol Chem, 279, pp. 54275-54282 ;\n van der Meer, F.J., van Tilburg, N.H., van Wijngaarden, A., van der Linden, I.K., Briet, E., Bertina, R.M., A second plasma inhibitor of activated protein C: Alpha 1-antitrypsin (1989) Thromb Haemost, 62, pp. 756-762 ;\n Al-Omari, M., Korenbaum, E., Ballmaier, M., Acute-phase protein alpha1-antitrypsin inhibits neutrophil calpain I and induces random migration (2011) Mol Med, 17, pp. 865-874 ;\n Schechter, I., Berger, A., On the size of the active site in proteases. I. Papain (1967) Biochem Biophys Res Commun, 27, pp. 157-162 ;\n Kounnas, M.Z., Church, F.C., Argraves, W.S., Strickland, D.K., Cellular internalization and degradation of antithrombin III-thrombin, heparin cofactor II-thrombin, and alpha 1-antitrypsin-trypsin complexes is mediated by the low density lipoprotein receptor-related protein (1996) J Biol Chem, 271, pp. 6523-6529 ;\n Strickland, D.K., Ranganathan, S., Diverse role of LDL receptor-related protein in the clearance of proteases and in signaling (2003) J Thromb Haemost, 1, pp. 1663-1670 ;\n Dementiev, A., Simonovic, M., Volz, K., Gettins, P.G., Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases (2003) J Biol Chem, 278, pp. 37881-37887 ;\n Huntington, J.A., Read, J.R., Carrell, R.W., Structure of a serpin-protease complex shows inhibition by deformation (2000) Nature, 407, pp. 923-926 ;\n Dementiev, A., Dobo, J., Gettins, P.G., Active site distortion is sufficient for proteinase inhibition by serpins: Structure of the covalent complex of alpha1-proteinase inhibitor with porcine pancreatic elastase (2006) J Biol Chem, 281, pp. 3452-3457 ;\n Stratikos, E., Gettins, P.G., Formation of the covalent serpin-proteinase complex involves translocation of the proteinase by more than 70 A and full insertion of the reactive center loop into beta-sheet A (1999) Proc Natl Acad Sci U S A, 96, pp. 4808-4813 ;\n Hopkins, P.C., Stone, S.R., The contribution of the conserved hinge region residues of alpha1-antitrypsin to its reaction with elastase (1995) Biochemistry, 34, pp. 15872-15879 ;\n Hood, D.B., Huntington, J.A., Gettins, P.G., Alpha 1-proteinase inhibitor variant T345R. Influence of P14 residue on substrate and inhibitory pathways (1994) Biochemistry, 33, pp. 8538-8547 ;\n Lawrence, D.A., Olson, S.T., Muhammad, S., Partitioning of serpin-proteinase reactions between stable inhibition and substrate cleavage is regulated by the rate of serpin reactive center loop insertion into beta-sheet A (2000) J Biol Chem, 275, pp. 5839-5844 ;\n Kaslik, G., Kardos, J., Szabo, E., Effects of serpin binding on the target proteinase: Global stabilization, localized increased structural flexibility, and conserved hydrogen bonding at the active site (1997) Biochemistry, 36, pp. 5455-5464 ;\n Zhou, A., Carrell, R.W., Huntington, J.A., The serpin inhibitory mechanism is critically dependent on the length of the reactive center loop (2001) J Biol Chem, 276, pp. 27541-27547 ;\n Im, H., Ahn, H.Y., Yu, M.H., Bypassing the kinetic trap of serpin protein folding by loop extension (2000) Protein Sci, 9, pp. 1497-1502 ;\n Gettins, P.G., Olson, S.T., Inhibitory serpins. New insights into their folding, polymerization, regulation and clearance (2016) Biochem J, 473, pp. 2273-2293 ;\n Bottomley, S.P., Lawrenson, I.D., Tew, D., Dai, W., Whisstock, J.C., Pike, R.N., The role of strand 1 of the C beta-sheet in the structure and function of alpha(1)-antitrypsin (2001) Protein Sci, 10, pp. 2518-2524 ;\n Quinsey, N.S., Fitton, H.L., Coughlin, P., Introduction of a mutation in the shutter region of antithrombin (Phe77 → Leu) increases affinity for heparin and decreases thermal stability (2003) Biochemistry, 42, pp. 10169-10173 ;\n Bottomley, S.P., Stone, S.R., Protein engineering of chimeric serpins: An investigation into effects of the serpin scaffold and reactive centre loop length (1998) Protein Eng, 11, pp. 1243-1247 ;\n Filion, M.L., Bhakta, V., Nguyen, L.H., Liaw, P.S., Sheffield, W.P., Full or partial substitution of the reactive center loop of alpha-1-proteinase inhibitor by that of heparin cofactor II: P1 Arg is required for maximal thrombin inhibition (2004) Biochemistry, 43, pp. 14864-14872 ;\n Chaillan-Huntington, C.E., Gettins, P.G., Huntington, J.A., Patston, P.A., The P6-P2 region of serpins is critical for proteinase inhibition and complex stability (1997) Biochemistry, 36, pp. 9562-9570 ;\n Plotnick, M.I., Schechter, N.M., Wang, Z.M., Liu, X., Rubin, H., Role of the P6-P3' region of the serpin reactive loop in the formation and breakdown of the inhibitory complex (1997) Biochemistry, 36, pp. 14601-14608 ;\n Andersen, O.J., Risor, M.W., Poulsen, E.C., Reactive center loop insertion in alpha-1-antitrypsin captured by accelerated molecular dynamics simulation (2017) Biochemistry, 56, pp. 634-646 ;\n Olson, S.T., Bjork, I., Shore, J.D., Kinetic characterization of heparin-catalyzed and uncatalyzed inhibition of blood coagulation proteinases by antithrombin (1993) Methods Enzymol, 222, pp. 525-559 ;\n Sutherland, J.S., Bhakta, V., Filion, M.L., Sheffield, W.P., The transferable tail: Fusion of the N-terminal acidic extension of heparin cofactor II to alpha1-proteinase inhibitor M358R specifically increases the rate of thrombin inhibition (2006) Biochemistry, 45, pp. 11444-11452 ;\n Scott, B.M., Matochko, W.L., Gierczak, R.F., Bhakta, V., Derda, R., Sheffield, W.P., Phage display of the serpin alpha-1 proteinase inhibitor randomized at consecutive residues in the reactive Centre loop and biopanned with or without thrombin (2014) PLoS One, 9 ;\n Kwon, K.S., Kim, J., Shin, H.S., Yu, M.H., Single amino acid substitutions of alpha 1-antitrypsin that confer enhancement in thermal stability (1994) J Biol Chem, 269, pp. 9627-9631 ;\n Kim, J., Lee, K.N., Yi, G.S., Yu, M.H., A thermostable mutation located at the hydrophobic core of alpha 1-antitrypsin suppresses the folding defect of the Z-type variant (1995) J Biol Chem, 270, pp. 8597-8601 ;\n Irving, J.A., Haq, I., Dickens, J.A., Faull, S.V., Lomas, D.A., Altered native stability is the dominant basis for susceptibility of alpha1-antitrypsin mutants to polymerization (2014) Biochem J, 460, pp. 103-115 ;\n Lee, K.N., Im, H., Kang, S.W., Yu, M.H., Characterization of a human alpha1-antitrypsin variant that is as stable as ovalbumin (1998) J Biol Chem, 273, pp. 2509-2516 ;\n Lee, K.N., Park, S.D., Yu, M.H., Probing the native strain in alpha1-antitrypsin (1996) Nat Struct Biol, 3, pp. 497-500 ;\n Seo, E.J., Im, H., Maeng, J.S., Kim, K.E., Yu, M.H., Distribution of the native strain in human alpha 1-antitrypsin and its association with protease inhibitor function (2000) J Biol Chem, 275, pp. 16904-16909 ;\n Shin, J.S., Ryu, S.H., Lee, C., Yu, M.H., Misfolding-assisted selection of stable protein variants using phage displays (2006) J Biochem Mol Biol, 39, pp. 55-60 ;\n Griffiths, S.W., King, J., Cooney, C.L., The reactivity and oxidation pathway of cysteine 232 in recombinant human alpha 1-antitrypsin (2002) J Biol Chem, 277, pp. 25486-25492 ;\n Bottomley, S.P., Hopkins, P.C., Whisstock, J.C., Alpha 1-antitrypsin polymerisation can occur by both loop A and C sheet mechanisms (1998) Biochem Biophys Res Commun, 251, pp. 1-5 ;\n Peterson, F.C., Gordon, N.C., Gettins, P.G., Formation of a noncovalent serpin-proteinase complex involves no conformational change in the serpin. Use of 1H-15N HSQC NMR as a sensitive nonperturbing monitor of conformation (2000) Biochemistry, 39, pp. 11884-11892 ;\n Porebski, B.T., Keleher, S., Hollins, J.J., Smoothing a rugged protein folding landscape by sequence-based redesign (2016) Sci Rep, 6 ;\n Yang, L., Irving, J.A., Dai, W., Aguilar, M.I., Bottomley, S.P., Probing the folding pathway of a consensus serpin using single tryptophan mutants (2018) Sci Rep, 8, p. 2121 ;\n Marijanovic, E.M., Fodor, J., Riley, B.T., Reactive centre loop dynamics and serpin specificity (2019) Sci Rep, 9, p. 3870 ;\n Pearce, M.C., Cabrita, L.D., Production of recombinant serpins in Escherichia coli (2011) Methods Enzymol, 501, pp. 13-28 ;\n Courtney, M., Buchwalder, A., Tessier, L.H., High-level production of biologically active human alpha 1-antitrypsin in Escherichia coli (1984) Proc Natl Acad Sci U S A, 81, pp. 669-673 ;\n Tessier, L.H., Jallat, S., Sauvageot, M., Crystal, R.G., Courtney, M., RNA structural elements for expression in Escherichia coli. Alpha 1-antitrypsin synthesis using translation control elements based on the cII ribosome-binding site of phage lambda (1986) FEBS Lett, 208, pp. 183-188 ;\n Johansen, H., Sutiphong, J., Sathe, G., High-level production of fully active human alpha 1-antitrypsin in Escherichia coli (1987) Mol Biol Med, 4, pp. 291-305 ;\n Sutiphong, J., Johansen, H., Sathe, G., Rosenberg, G.S., Shatzman, A., Selection of mutations that increase alpha 1-antitrypsin gene expression in Escherichia coli (1987) Mol Biol Med, 4, pp. 307-322 ;\n Schulze, A.J., Degryse, E., Speck, D., Huber, R., Bischoff, R., Expression of alpha 1-proteinase inhibitor in Escherichia coli: Effects of single amino acid substitutions in the active site loop on aggregate formation (1994) J Biotechnol, 32, pp. 231-238 ;\n Haq, I., Irving, J.A., Faull, S.V., Reactive Centre loop mutants of alpha-1-antitrypsin reveal position-specific effects on intermediate formation along the polymerization pathway (2013) Biosci Rep, 33 ;\n Schulze, A.J., Huber, R., Degryse, E., Speck, D., Bischoff, R., Inhibitory activity and conformational transition of alpha 1-proteinase inhibitor variants (1991) Eur J Biochem, 202, pp. 1147-1155 ;\n Curtis, H., Sandoval, C., Oblin, C., Difalco, M.R., Congote, L.F., Insect cell production of a secreted form of human alpha(1)-proteinase inhibitor as a bifunctional protein which inhibits neutrophil elastase and has growth factor-like activities (2002) J Biotechnol, 93, pp. 35-44 ;\n Sandoval, C., Curtis, H., Congote, L.F., Enhanced proliferative effects of a baculovirus-produced fusion protein of insulin-like growth factor and alpha(1)-proteinase inhibitor and improved anti-elastase activity of the inhibitor with glutamate at position 351 (2002) Protein Eng, 15, pp. 413-418 ;\n Agarwal, S., Jha, S., Sanyal, I., Amla, D.V., Expression and purification of recombinant human alpha1-proteinase inhibitor and its single amino acid substituted variants in Escherichia coli for enhanced stability and biological activity (2010) J Biotechnol, 147, pp. 64-72 ;\n Kang, H.A., Nam, S.W., Kwon, K.S., Chung, B.H., Yu, M.H., High-level secretion of human alpha 1-antitrypsin from Saccharomyces cerevisiae using inulinase signal sequence (1996) J Biotechnol, 48, pp. 15-24 ;\n Agarwal, S., Singh, R., Sanyal, I., Amla, D.V., Expression of modified gene encoding functional human alpha-1-antitrypsin protein in transgenic tomato plants (2008) Transgenic Res, 17, pp. 881-896 ;\n Zhang, N., Wright, T., Caraway, P., Xu, J., Enhanced secretion of human alpha1-antitrypsin expressed with a novel glycosylation module in tobacco BY-2 cell culture (2019) Bioengineered, 10, pp. 87-97 ;\n Paterson, T., Innes, J., Moore, S., Approaches to maximizing stable expression of alpha 1-antitrypsin in transformed CHO cells (1994) Appl Microbiol Biotechnol, 40, pp. 691-698 ;\n Blanchard, V., Liu, X., Eigel, S., N-glycosylation and biological activity of recombinant human alpha1-antitrypsin expressed in a novel human neuronal cell line (2011) Biotechnol Bioeng, 108, pp. 2118-2128 ;\n Amann, T., Hansen, A.H., Kol, S., Glyco-engineered CHO cell lines producing alpha-1-antitrypsin and C1 esterase inhibitor with fully humanized N-glycosylation profiles (2019) Metab Eng, 52, pp. 143-152 ;\n Janus, E.D., Phillips, N.T., Carrell, R.W., Smoking, lung function, and alpha 1-antitrypsin deficiency (1985) Lancet, 1, pp. 152-154 ;\n Li, Z., Alam, S., Wang, J., Sandstrom, C.S., Janciauskiene, S., Mahadeva, R., Oxidized {alpha}1-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: Potential role in emphysema (2009) Am J Physiol Lung Cell Mol Physiol, 297, pp. L388-L400 ;\n Taggart, C., Cervantes-Laurean, D., Kim, G., Oxidation of either methionine 351 or methionine 358 in alpha 1-antitrypsin causes loss of anti-neutrophil elastase activity (2000) J Biol Chem, 275, pp. 27258-27265 ;\n Travis, J., Owen, M., George, P., Isolation and properties of recombinant DNA produced variants of human alpha 1-proteinase inhibitor (1985) J Biol Chem, 260, pp. 4384-4389 ;\n Jallat, S., Carvallo, D., Tessier, L.H., Altered specificities of genetically engineered alpha 1 antitrypsin variants (1986) Protein Eng, 1, pp. 29-35 ;\n Silberstein, D.Z., Karuppanan, K., Aung, H.H., Chen, C.H., Cross, C.E., McDonald, K.A., An oxidation-resistant, recombinant alpha-1 antitrypsin produced in Nicotiana benthamiana (2018) Free Radic Biol Med, 120, pp. 303-310 ;\n Zhu, W., Li, L., Deng, M., Oxidation-resistant and thermostable forms of alpha-1 antitrypsin from Escherichia coli inclusion bodies (2018) FEBS Open Bio, 8, pp. 1711-1721 ;\n Lewis, J.H., Iammarino, R.M., Spero, J.A., Hasiba, U., Antithrombin Pittsburgh: An alpha1-antitrypsin variant causing hemorrhagic disease (1978) Blood, 51, pp. 129-137 ;\n Owen, M., Brennan, S., Lewis, J., Carrell, R., Mutation of antitrypsin to antithrombin. Alpha 1-antitrypsin Pittsburgh (358 Met leads to Arg), a fatal bleeding disorder (1983) N Engl J Med, 309, pp. 649-698 ;\n Scott, C.F., Carrell, R.W., Glaser, C.B., Kueppers, F., Lewis, J.H., Colman, R.W., Alpha-1-antitrypsin-Pittsburgh. A potent inhibitor of human plasma factor XIa, kallikrein, and factor XIIf (1986) J Clin Invest, 77, pp. 631-634 ;\n Colman, R.W., Flores, D.N., De La Cadena, R.A., Recombinant alpha 1-antitrypsin Pittsburgh attenuates experimental gram-negative septicemia (1988) Am J Pathol, 130, pp. 418-426 ;\n Harper, P.L., Taylor, F.B., DeLa Cadena, R.A., Courtney, M., Colman, R.W., Carrell, R.W., Recombinant antitrypsin Pittsburgh undergoes proteolytic cleavage during E. coli sepsis and fails to prevent the associated coagulopathy in a primate model (1998) Thromb Haemost, 80, pp. 816-821 ;\n Heeb, M.J., Bischoff, R., Courtney, M., Griffin, J.H., Inhibition of activated protein C by recombinant alpha 1-antitrypsin variants with substitution of arginine or leucine for methionine358 (1990) J Biol Chem, 265, pp. 2365-2369 ;\n Hopkins, P.C., Crowther, D.C., Carrell, R.W., Stone, S.R., Development of a novel recombinant serpin with potential antithrombotic properties (1995) J Biol Chem, 270, pp. 11866-11871 ;\n Hopkins, P.C., Pike, R.N., Stone, S.R., Evolution of serpin specificity: Cooperative interactions in the reactive-site loop sequence of antithrombin specifically restrict the inhibition of activated protein C (2000) J Mol Evol, 51, pp. 507-515 ;\n Sutherland, J.S., Bhakta, V., Sheffield, W.P., The appended tail region of heparin cofactor II and additional reactive Centre loop mutations combine to increase the reactivity and specificity of alpha1-proteinase inhibitor M358R for thrombin (2007) Thromb Haemost, 98, pp. 1014-1023 ;\n Sheffield, W.P., Eltringham-Smith, L.J., Bhakta, V., Gataiance, S., Reduction of thrombus size in murine models of thrombosis following administration of recombinant alpha1-proteinase inhibitor mutant proteins (2012) Thromb Haemost, 107, pp. 972-984 ;\n Roddick, L.A., Bhakta, V., Sheffield, W.P., Fusion of the C-terminal triskaidecapeptide of hirudin variant 3 to alpha1-proteinase inhibitor M358R increases the serpin-mediated rate of thrombin inhibition (2013) BMC Biochem, 14, p. 31 ;\n de Souza, L.R., Scott, B.M., Bhakta, V., Donkor, D.A., Perruzza, D.L., Sheffield, W.P., Serpin phage display: The use of a T7 system to probe reactive center loop libraries with different serine proteinases (2018) Methods Mol Biol, 1826, pp. 41-64 ;\n Izaguirre, G., Rezaie, A.R., Olson, S.T., Engineering functional antithrombin exosites in alpha1-proteinase inhibitor that specifically promote the inhibition of factor Xa and factor IXa (2009) J Biol Chem, 284, pp. 1550-1558 ;\n Izaguirre, G., Olson, S.T., Residues Tyr253 and Glu255 in strand 3 of beta-sheet C of antithrombin are key determinants of an exosite made accessible by heparin activation to promote rapid inhibition of factors Xa and IXa (2006) J Biol Chem, 281, pp. 13424-13432 ;\n Yang, L., Dinarvand, P., Qureshi, S.H., Rezaie, A.R., Engineering D-helix of antithrombin in alpha-1-proteinase inhibitor confers antiinflammatory properties on the chimeric serpin (2014) Thromb Haemost, 112, pp. 164-175 ;\n Polderdijk, S.G., Adams, T.E., Ivanciu, L., Camire, R.M., Baglin, T.P., Huntington, J.A., Design and characterization of an APC-specific serpin for the treatment of hemophilia (2017) Blood, 129, pp. 105-113 ;\n Shapiro, A.D., Mitchell, I.S., Nasr, S., The future of bypassing agents for hemophilia with inhibitors in the era of novel agents (2018) J Thromb Haemost, 16, pp. 2362-2374 ;\n Polderdijk, S.G.I., Huntington, J.A., Identification of serpins specific for activated protein C using a lysate-based screening assay (2018) Sci Rep, 8 ;\n de Maat, S., Sanrattana, W., Mailer, R.K., Design and characterization of alpha1-antitrypsin variants for treatment of contact system-driven thromboinflammation (2019) Blood, 134 (19), pp. 1658-1669. , https://doi.org/10.1182/blood.2019000481 ;\n Schapira, M., Ramus, M.A., Waeber, B., Protection by recombinant alpha 1-antitrypsin Ala357 Arg358 against arterial hypotension induced by factor XII fragment (1987) J Clin Invest, 80, pp. 582-585 ;\n Sulikowski, T., Bauer, B.A., Patston, P.A., Alpha(1)-proteinase inhibitor mutants with specificity for plasma kallikrein and C1s but not C1 (2002) Protein Sci, 11, pp. 2230-2236 ;\n Thomas, G., Furin at the cutting edge: From protein traffic to embryogenesis and disease (2002) Nat Rev Mol Cell Biol, 3, pp. 753-766 ;\n Anderson, E.D., Thomas, L., Hayflick, J.S., Thomas, G., Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant (1993) J Biol Chem, 268, pp. 24887-24891 ;\n Bahbouhi, B., Bendjennat, M., Guetard, D., Seidah, N.G., Bahraoui, E., Effect of alpha-1 antitrypsin Portland variant (alpha 1-PDX) on HIV-1 replication (2000) Biochem J, 352, pp. 91-98 ;\n Watanabe, M., Hirano, A., Stenglein, S., Nelson, J., Thomas, G., Wong, T.C., Engineered serine protease inhibitor prevents furin-catalyzed activation of the fusion glycoprotein and production of infectious measles virus (1995) J Virol, 69, pp. 3206-3210 ;\n Bassi, D.E., Lopez De Cicco, R., Mahloogi, H., Zucker, S., Thomas, G., Klein-Szanto, A.J., Furin inhibition results in absent or decreased invasiveness and tumorigenicity of human cancer cells (2001) Proc Natl Acad Sci U S A, 98, pp. 10326-10331 ;\n Yakala, G.K., Cabrera-Fuentes, H.A., Crespo-Avilan, G.E., FURIN inhibition reduces vascular remodeling and atherosclerotic lesion progression in mice (2019) Arterioscler Thromb Vasc Biol, 39, pp. 387-401 ;\n Dufour, E.K., Desilets, A., Longpre, J.M., Leduc, R., Stability of mutant serpin/furin complexes: Dependence on pH and regulation at the deacylation step (2005) Protein Sci, 14, pp. 303-315 ;\n Tsuji, A., Kanie, H., Makise, H., Yuasa, K., Nagahama, M., Matsuda, Y., Engineering of alpha1-antitrypsin variants selective for subtilisin-like proprotein convertases PACE4 and PC6: Importance of the P2' residue in stable complex formation of the serpin with proprotein convertase (2007) Protein Eng Des Sel, 20, pp. 163-170 ;\n Izaguirre, G., Qi, L., Lima, M., Olson, S.T., Identification of serpin determinants of specificity and selectivity for furin inhibition through studies of alpha1PDX (alpha1-protease inhibitor Portland)-serpin B8 and furin active-site loop chimeras (2013) J Biol Chem, 288, pp. 21802-21814 ;\n Izaguirre, G., Arciniega, M., Quezada, A.G., Specific and selective inhibitors of proprotein convertases engineered by transferring serpin B8 reactive-site and exosite determinants of reactivity to the serpin alpha1PDX (2019) Biochemistry, 58, pp. 1679-1688 ;\n Irving, J.A., Pike, R.N., Dai, W., Evidence that serpin architecture intrinsically supports papain-like cysteine protease inhibition: Engineering alpha(1)-antitrypsin to inhibit cathepsin proteases (2002) Biochemistry, 41, pp. 4998-5004 ;\n Campos, M.A., Kueppers, F., Stocks, J.M., Safety and pharmacokinetics of 120 mg/kg versus 60 mg/kg weekly intravenous infusions of alpha-1 proteinase inhibitor in alpha-1 antitrypsin deficiency: A multicenter, randomized, double-blind, crossover study (SPARK) (2013) COPD, 10, pp. 687-695 ;\n Cantin, A.M., Woods, D.E., Cloutier, D., Dufour, E.K., Leduc, R., Polyethylene glycol conjugation at Cys232 prolongs the half-life of alpha1 proteinase inhibitor (2002) Am J Respir Cell Mol Biol, 27, pp. 659-665 ;\n Lindhout, T., Iqbal, U., Willis, L.M., Site-specific enzymatic polysialylation of therapeutic proteins using bacterial enzymes (2011) Proc Natl Acad Sci U S A, 108, pp. 7397-7402 ;\n Lusch, A., Kaup, M., Marx, U., Tauber, R., Blanchard, V., Berger, M., Development and analysis of alpha 1-antitrypsin neoglycoproteins: The impact of additional N-glycosylation sites on serum half-life (2013) Mol Pharm, 10, pp. 2616-2629 ;\n Chung, H.S., Kim, J.S., Lee, S.M., Park, S.J., Additional N-glycosylation in the N-terminal region of recombinant human alpha-1 antitrypsin enhances the circulatory half-life in Sprague-Dawley rats (2016) Glycoconj J, 33, pp. 201-208 ;\n Rath, T., Baker, K., Dumont, J.A., Fc-fusion proteins and FcRn: Structural insights for longer-lasting and more effective therapeutics (2015) Crit Rev Biotechnol, 35, pp. 235-254 ;\n Lee, S., Lee, Y., Hong, K., Effect of recombinant alpha1-antitrypsin Fc-fused (AAT-Fc)protein on the inhibition of inflammatory cytokine production and streptozotocin-induced diabetes (2013) Mol Med, 19, pp. 65-71 ;\n Jonigk, D., Al-Omari, M., Maegel, L., Anti-inflammatory and immunomodulatory properties of alpha1-antitrypsin without inhibition of elastase (2013) Proc Natl Acad Sci U S A, 110, pp. 15007-15012 ;\n Toldo, S., Mauro, A.G., Marchetti, C., Recombinant human alpha-1 antitrypsin-fc fusion protein reduces mouse myocardial inflammatory injury after ischemia-reperfusion independent of elastase inhibition (2016) J Cardiovasc Pharmacol, 68, pp. 27-32 ;\n Joosten, L.A., Crisan, T.O., Azam, T., Alpha-1-anti-trypsin-fc fusion protein ameliorates gouty arthritis by reducing release and extracellular processing of IL-1beta and by the induction of endogenous IL-1Ra (2016) Ann Rheum Dis, 75, pp. 1219-1227 ;\n https://clinicaltrials.gov/ct2/show/NCT04073498, [accessed October 22, 2019] ;\n PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency. [accessed October 21, 2019], , https://ClinicalTrials.gov/show/NCT03815396 ;\n Tardif, J.C., L'Allier, P.L., Gregoire, J., A randomized controlled, phase 2 trial of the viral serpin Serp-1 in patients with acute coronary syndromes undergoing percutaneous coronary intervention (2010) Circ Cardiovasc Interv, 3, pp. 543-548 ;\n Chaillan-Huntington, C.E., Patston, P.A., Influence of the P5 residue on alpha1-proteinase inhibitor mechanism (1998) J Biol Chem, 273, pp. 4569-4573", "hasCitationDuplums" : false, "userChangeableUntil" : "2020-11-23T14:48:34.612+0000", "directInstitutesForSort" : "", "ownerAuthorCount" : 4, "ownerInstituteCount" : 20, "directInstituteCount" : 0, "authorCount" : 2, "contributorCount" : 0, "hasQualityFactor" : true, "link" : "/api/publication/31414281", "label" : "Scott B.M. et al. Engineering the serpin α1-antitrypsin: A diversity of goals and techniques. (2020) PROTEIN SCIENCE 0961-8368 1469-896X 29 4 856-871", "template" : "