Insights into lid movements of Burkholderia cepacia lipase inferred from molecular dynamics simulations

Citations Over TimeTop 13% of 2009 papers

Abstract

The interfacial activation of many lipases at water/lipid interface is mediated by large conformational changes of a so-called lid subdomain that covers up the enzyme active site. Here we investigated using molecular dynamic simulations in different explicit solvent environments (water, octane and water/octane interface) the molecular mechanism by which the lid motion of Burkholderia cepacia lipase might operate. Although B. cepacia lipase has so far only been crystallized in open conformation, this study reveals for the first time the major conformational rearrangements that the enzyme undergoes under the influence of the solvent, which either exposes or shields the active site from the substrate. In aqueous media, the lid switches from an open to a closed conformation while the reverse motion occurs in organic environment. In particular, the role of a subdomain facing the lid on B. cepacia lipase conformational rearrangements was investigated using position-restrained MD simulations. Our conclusions indicate that the sole mobility of alpha9 helix side-chains of B. cepacia lipase is required for the full completion of the lid conformational change which is essentially driven by alpha5 helix movement. The role of selected alpha5 hydrophobic residues on the lid movement was further examined. In silico mutations of two residues, V138 and F142, were shown to drastically modify the conformational behavior of B. cepacia lipase. Overall, our results provide valuable insight into the role played by the surrounding environment on the lid conformational rearrangement and the activation of B. cepacia lipase.

Related Papers

• → Improving catalytic performance of Burkholderia cepacia lipase immobilized on macroporous resin NKA(2011)106 cited
• → Esterification activity and conformation studies of Burkholderia cepacia lipase in conventional organic solvents, ionic liquids and their co-solvent mixture media(2010)79 cited
• → Screening of Bacteria Producing Lipase from Insect Gut: Isolation and Characterization of a Strain, Burkholderia sp. HY-10 Producing Lipase(2007)7 cited
• → Characterization of a Novel Lipase from the Soil Isolate-Burkholderia cepacia SS-16(2000)1 cited
• 곤충 장내미생물로부터 lipase 생산능력이 우수한 Burkholderia sp. HY-10 균주의 분리 및 특성(2007)