Pretražite po imenu i prezimenu autora, mentora, urednika, prevoditelja

Napredna pretraga

Pregled bibliografske jedinice broj: 1067318

The substrate selectivity of the two homologous SGNH hydrolases from Streptomyces bacteria: Molecular dynamics and experimental study


Maršavelski, Aleksandra; Sabljić, Igor; Sugimori, Daisuke; Kojić-Prodić, Biserka
The substrate selectivity of the two homologous SGNH hydrolases from Streptomyces bacteria: Molecular dynamics and experimental study // International journal of biological macromolecules, 158 (2020), 222-230 doi:10.1016/j.ijbiomac.2020.04.198 (međunarodna recenzija, članak, znanstveni)


Naslov
The substrate selectivity of the two homologous SGNH hydrolases from Streptomyces bacteria: Molecular dynamics and experimental study

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

Izvornik
International journal of biological macromolecules (0141-8130) 158 (2020); 222-230

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

Ključne riječi
Lipids ; Phospholipids ; Substrate specificity ; Enzyme promiscuity ; SGNH hydrolases ; Molecular dynamics simulations (MD)

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 get insight into binding modes of phospholipid and triglyceride substrates in both enzymes and understand their chain-length preferences, we opted for computational approach based on in silico prepared enzyme-substrate complexes. Docking procedure and molecular dynamics simulations at microsecond time scale were applied. The modelled complexes of SaPLA1 and SrLip enzymes revealed substrate accommodation: a) the acyl-chain attached to sn-1 position fits into the hydrophobic pocket, b) the acyl-chain attached to sn-2 position fits in the hydrophobic cleft, whereas c) the sn-3 bound acyl chain of the triglyceride or polar head of the glycerophospholipid fits into the binding groove. Moreover, our results pinpointed subtle amino acid differences in the hydrophobic pockets of these two enzymes 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


Projekt / tema
JP15K05557
JP20K05822

Ustanove
Institut "Ruđer Bošković", Zagreb,
Prirodoslovno-matematički fakultet, Zagreb

Citiraj ovu publikaciju

Maršavelski, Aleksandra; Sabljić, Igor; Sugimori, Daisuke; Kojić-Prodić, Biserka
The substrate selectivity of the two homologous SGNH hydrolases from Streptomyces bacteria: Molecular dynamics and experimental study // International journal of biological macromolecules, 158 (2020), 222-230 doi:10.1016/j.ijbiomac.2020.04.198 (međunarodna recenzija, članak, znanstveni)
Maršavelski, A., Sabljić, I., Sugimori, D. & Kojić-Prodić, B. (2020) The substrate selectivity of the two homologous SGNH hydrolases from Streptomyces bacteria: Molecular dynamics and experimental study. International journal of biological macromolecules, 158, 222-230 doi:10.1016/j.ijbiomac.2020.04.198.
@article{article, year = {2020}, pages = {222-230}, DOI = {10.1016/j.ijbiomac.2020.04.198}, keywords = {Lipids, Phospholipids, Substrate specificity, Enzyme promiscuity, SGNH hydrolases, Molecular dynamics simulations (MD)}, journal = {International journal of biological macromolecules}, doi = {10.1016/j.ijbiomac.2020.04.198}, volume = {158}, issn = {0141-8130}, title = {The substrate selectivity of the two homologous SGNH hydrolases from Streptomyces bacteria: Molecular dynamics and experimental study}, keyword = {Lipids, Phospholipids, Substrate specificity, Enzyme promiscuity, SGNH hydrolases, Molecular dynamics simulations (MD)} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Citati