Naslov
Understanding substrate promiscuity by computational approach: a case study of selected phospholipase and lipase

Autori
Aleksandra Maršavelski, Igor Sabljić, Daisuke Sugimori, Biserka Kojić-Prodić

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
ELIXIR 3D BioInfo Community Annual Meeting, https://elixir-europe.org/events/3d-bioinfo-2021- annual-meeting

Mjesto i datum
Online, 02.11.2021. - 04.11.2021

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
SGNH hydrolase superfamily, phospholipase A1, MD simulations

Sažetak
Two extracellular enzymes of the SGNH hydrolase superfamily reveal highly homologous 3D structures, but act on different substrates ; one is a true phospholipase A1 from Streptomyces albidoflavus (SaPLA1, EC: 3.1.1.32, PDB code: 4HYQ), whereas the promiscuous enzyme from Streptomyces rimosus (SrLip, EC: 3.1.1.3, PDB code: 5MAL) exhibits lipase, phospholipase, esterase, thioesterase, and Tweenase activities. To understand binding modes of phospholipid and triglyceride substrates in both enzymes and their chain-length preferences, we opted for a computational approach based on in silico prepared enzyme-substrate complexes. Our results pinpointed subtle amino acid differences in the hydrophobic pockets which accommodate the acyl chain attached to sn-1 position of glycerol to be responsible for the chain length preference. Slight differences in the binding grooves of SaPLA1 and SrLip, which accommodate the acyl chain attached to sn-3 position are responsible for exclusive phospholipase and both phospholipase/lipase activities of these two enzymes, respectively. The results of modelling correlate with the experimentally obtained kinetic parameters given in the literature and are important for protein engineering that aims to obtain a variant of enzyme, which would preferably act on the substrate of interest.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA