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Construction of an engineered alpha 1-antitrypsin with inhibitory activity based on theoretical studies
Sangachini, Elham Dasi; Hasannia, Sadegh; Taghdir, Majid; Pirooznia, Nazanin; Ghadicholaei, Kamran Khalili.
Afiliação
  • Sangachini, Elham Dasi; University of Guilan. Faculty of Science. Department of Biology. Rasht. IR
  • Hasannia, Sadegh; Tarbiat Modares University. Faculty of Biological Sciences. Tehran. IR
  • Taghdir, Majid; University of Guilan. Faculty of Science. Department of Biology. Rasht. IR
  • Pirooznia, Nazanin; University of Guilan. Faculty of Science. Department of Biology. Rasht. IR
  • Ghadicholaei, Kamran Khalili; University of Guilan. Faculty of Science. Department of Biology. Rasht. IR
Electron. j. biotechnol ; 15(2): 8-8, Mar. 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-640543
Biblioteca responsável: CL1.1
ABSTRACT

Background:

The elastase inhibitor alpha-1-antitrypsin (AAT), is a member of the serpin superfamily of protease inhibitors. AAT has a characteristic secondary structure of three-beta-sheets, nine-alpha-helices and a reactive central loop (RCL). This protein inhibits target proteases by forming a stable complex in which the cleaved RCL is inserted into beta-sheet-A of the serpin, leading to a conformational change in the AAT protein. Spontaneous polymerization and instability of AAT are challenges with regard to producing drugs against AAT-deficient diseases. Therefore, the purpose of many investigations currently is to produce drugs with lower degrees of polymerization and higher stabilities. In order to investigate the effect of the N-terminal segment (residues 1-43) on AAT structure, molecular dynamic (MD) simulation was used to study structural properties including Root-mean-square deviation (RMSD), internal motions, intramolecular non-bonded interactions and the total accessible surface area (ASA) of native and reduced AAT. These properties were compared in native and truncated AAT.

Results:

Theoretical studies showed no noticeable differences in the dynamic and structural properties of the two structures. These findings provided the basis for the experimental phase of the study in which sequences from the two AAT constructs were inserted into the expression vector pGAPZ and transformed into Pichia pastoris. Results showed no differences in the activities and polymerization of the two AAT constructs.

Conclusions:

As small-scale medicines are preferred by lung drug delivery systems, in this study AAT was designed and constructed by decreasing the number of amino acids at the N-terminal region.
Assuntos


Texto completo: Disponível Coleções: Bases de dados internacionais Contexto em Saúde: Doenças Negligenciadas Problema de saúde: Hanseníase Base de dados: LILACS Assunto principal: Pichia / Inibidores da Tripsina / Alfa 1-Antitripsina / Simulação de Dinâmica Molecular Limite: Humanos Idioma: Inglês Revista: Electron. j. biotechnol Assunto da revista: Biotecnologia Ano de publicação: 2012 Tipo de documento: Artigo País de afiliação: Irã Instituição/País de afiliação: Tarbiat Modares University/IR / University of Guilan/IR

Texto completo: Disponível Coleções: Bases de dados internacionais Contexto em Saúde: Doenças Negligenciadas Problema de saúde: Hanseníase Base de dados: LILACS Assunto principal: Pichia / Inibidores da Tripsina / Alfa 1-Antitripsina / Simulação de Dinâmica Molecular Limite: Humanos Idioma: Inglês Revista: Electron. j. biotechnol Assunto da revista: Biotecnologia Ano de publicação: 2012 Tipo de documento: Artigo País de afiliação: Irã Instituição/País de afiliação: Tarbiat Modares University/IR / University of Guilan/IR
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