Naslov
Relevant Interdomain and Active Site Interactions in the Autotransporter Esterase EstA from Pseudomonas aeruginosa

Autori
Mrnjavac, Natalia ; Vazdar, Mario ; Bertoša, Branimir

Izvornik
Molecular simulation (0892-7022) 46 (2020), 10; 743-756

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Molecular dynamics simulations (MD) ; autotransporter esterase EstA ; simulation of transmembrane protein in solvated lipid bilayer ; pseudomonas aeruginosa ; hydrogen bond networ

Sažetak
Structural and dynamical properties of the autotransporter esterase EstA from bacterium Pseudomonas aeruginosa were studied using molecular dynamics (MD) simulations. Four different systems, including the full-length EstA enzyme inserted into a solvated 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) lipid bilayer, as well as the solvated isolated passenger domain of EstA were simulated without ligand and in complex with 4 hydroxyphenyl octanoate bound as tetrahedral intermediate. Detailed analysis of non-covalent interactions was performed based on 100 ns long MD simulations. It was found that active site interactions include not only the catalytic triad (Ser14, Asp286, His289), but also a three-residue oxyanion hole (backbone of Ser14, Gly92 and Asn147), hydrophobic residues involved in tetrahedral intermediate stabilisation, and residues participating in the active site hydrogen bond network. Moreover, interactions between protein domains were analysed and it was found that interacting residues are located on specific structures not usually found in GDSL hydrolases or autotransporter β barrels. In case of full-length EstA enzyme, MD simulations point to specific interactions between the central and remote regions of the active site which are important for adequate intermediate stabilization.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija, Biologija

POVEZANOST RADA