Send to

Choose Destination
Proteins. 2017 Jul;85(7):1351-1361. doi: 10.1002/prot.25296. Epub 2017 Apr 19.

Crystal structure analysis, covalent docking, and molecular dynamics calculations reveal a conformational switch in PhaZ7 PHB depolymerase.

Author information

Department of Chemistry, National and Kapodistrian University of Athens, Athens, 15784, Greece.
Department of Chemistry, University of Ioannina, Ioannina, 45110, Greece.
Department of Chemistry, York College and the Graduate Center of the City University of New York, 94-20 Guy R. Brewer Blvd, Jamaica, New York, 11451.
Institut für Mikrobiologie, Universität Stuttgart, Allmandring 31, Stuttgart, 70550, Germany.
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, 20521, Finland.


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; 85:1351-1361.


X-ray crystallography; biopolymer; covalent docking; depolymerase; molecular dynamics simulations

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center