The microbial transglutaminase (TGase) from Streptomyces mobaraensis (MTGase) is widely used for industrial applications. However, in the last decades, TGases from other bacteria have been described. We focused our attention on TGase, from Kutzneria albida (KalbTGase), recently characterized as more selective than MTGase and proposed for applications in drug delivery. By comparison of the crystallo-graphic structures, the volume of the catalytic site results smaller in KalbTGase. We compared KalbTGase and MTGase structural flexibility by molecular dynamics (MD) simulations at different conditions. KalbTGase is more rigid than MTGase at 300 K, but the catalytic site has a preserved conformation in both structures. Preliminary studies at higher temperatures suggest that KalbTGase acquires enhanced conformational flexibility far from the active site region. The volume of the catalytic active site pocket of KalbTGase at room temperature is smaller than that of MTGase, and decreases at 335 K, remaining stable after further temperature increase. On the contrary, in MTGase the pocket volume continues to decrease as the temperature increases. Overall, the results of our study suggest that at room temperature the enhanced specificity of KalbTGase could be related to a more closed catalytic pocket and lower flexibility than MTGase. Moreover, by preliminary results at higher temperature, KalbTGase structural flexibility suggests an adaptability to different substrates not recognized at room temperature. Lower adaptability of MTGase at higher temperature with a reduction of the catalytic pocket, instead, suggests a reduction of its activity. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

Molecular dynamics analysis of the structural properties of the transglutaminases of Kutzneria albida and Streptomyces mobaraensis

Giordano, Deborah;Marabotti, Anna;Facchiano, Angelo
2022-01-01

Abstract

The microbial transglutaminase (TGase) from Streptomyces mobaraensis (MTGase) is widely used for industrial applications. However, in the last decades, TGases from other bacteria have been described. We focused our attention on TGase, from Kutzneria albida (KalbTGase), recently characterized as more selective than MTGase and proposed for applications in drug delivery. By comparison of the crystallo-graphic structures, the volume of the catalytic site results smaller in KalbTGase. We compared KalbTGase and MTGase structural flexibility by molecular dynamics (MD) simulations at different conditions. KalbTGase is more rigid than MTGase at 300 K, but the catalytic site has a preserved conformation in both structures. Preliminary studies at higher temperatures suggest that KalbTGase acquires enhanced conformational flexibility far from the active site region. The volume of the catalytic active site pocket of KalbTGase at room temperature is smaller than that of MTGase, and decreases at 335 K, remaining stable after further temperature increase. On the contrary, in MTGase the pocket volume continues to decrease as the temperature increases. Overall, the results of our study suggest that at room temperature the enhanced specificity of KalbTGase could be related to a more closed catalytic pocket and lower flexibility than MTGase. Moreover, by preliminary results at higher temperature, KalbTGase structural flexibility suggests an adaptability to different substrates not recognized at room temperature. Lower adaptability of MTGase at higher temperature with a reduction of the catalytic pocket, instead, suggests a reduction of its activity. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/4812192
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact