Crystal structure analysis, covalent docking, and molecular dynamics calculations reveal a conformational switch in PhaZ7 PHB depolymerase.
Proteins
; 85(7): 1351-1361, 2017 07.
Article
em En
| MEDLINE
| ID: mdl-28370478
ABSTRACT
An open and a closed conformation of a surface loop in PhaZ7 extracellular poly(3-hydroxybutyrate) depolymerase were identified in two high-resolution crystal structures of a PhaZ7 Y105E mutant. Molecular dynamics (MD) simulations revealed high root mean square fluctuations (RMSF) of the 281-295 loop, in particular at residue Asp289 (RMSF 7.62 Å). Covalent docking between a 3-hydroxybutyric acid trimer and the catalytic residue Ser136 showed that the binding energy of the substrate is significantly more favorable in the open loop conformation compared to that in the closed loop conformation. MD simulations with the substrate covalently bound depicted 1 Å RMSF higher values for the residues 281-295 in comparison to the apo (substrate-free) form. In addition, the presence of the substrate in the active site enhanced the ability of the loop to adopt a closed form. Taken together, the analysis suggests that the flexible loop 281-295 of PhaZ7 depolymerase can act as a lid domain to control substrate access to the active site of the enzyme. Proteins 2017; 851351-1361. © 2017 Wiley Periodicals, Inc.
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Base de dados:
MEDLINE
Assunto principal:
Poliésteres
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Proteínas de Bactérias
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Hidrolases de Éster Carboxílico
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Burkholderiaceae
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Simulação de Dinâmica Molecular
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Hidroxibutiratos
Idioma:
En
Revista:
Proteins
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Grécia