By a News Reporter-Staff News Editor at Life Science Weekly -- Investigators discuss new findings in Biophysics. According to news originating from Haryana, India, by NewsRx correspondents, research stated, "Serum paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-bound mammalian enzyme exhibiting antiatherosclerotic activity. Despite years of research, an accurate model for the binding interaction between PON1 and HDL has not been established."
Our news journalists obtained a quote from the research from National Dairy Research Institute, "However, it is reported that anchoring of PON1 to HDL is mainly governed by an N-terminal alpha helix H1 and another short helix H2. Here, we studied the molecular association of full-length human PON1 (huPON1) with a HDL-mimetic dipalmitoylphosphatidylcholine (DPPC) bilayer using homology modeling and molecular dynamics simulations. Our results indicate that H1 is the highly dynamic part of huPON1, showing clockwise rotation of up to 30A degrees within the DPPC bilayer. However, without phospholipid molecules, H1 experiences helical distortions, illustrating an incompatible HDL-anchoring conformation. Snorkeling interactions of K3, R18, and R27 together with aromatic locks formed by Y187, Y190, W194, and W202 are highly essential for anchoring of huPON1 to HDL's surface. Molecular mechanics/Poisson-Boltzmann solvent-accessible surface area (MM/PBSA) binding free energy calculation revealed that H1 displays greater binding affinity towards lipid molecules compared with H2 and H3, suggesting that H1 is the most probable HDL-binding domain of PON1. Binding free energy decomposition showed that K3, R18, and R27 interact with polar headgroups of DPPC membrane through electrostatic interaction. Moreover, Y187, Y190, W194, and W202 interact with DPPC lipids mainly through van der Waals interaction. Taken together, these results show that the transmembrane helix H1 along with the interfacial positively charged and aromatic resides were crucial for PON1's association with HDL particle."
According to the news editors, the research concluded: "The current study will be useful towards understanding the antiatherosclerotic and bioscavenging properties of this promiscuous enzyme."
For more information on this research see: Molecular dynamics simulation of human serum paraoxonase 1 in DPPC bilayer reveals a critical role of transmembrane helix H1 for HDL association. European Biophysics Journal with Biophysics Letters, 2014;43(1):35-51. European Biophysics Journal with Biophysics Letters can be contacted at: Springer, 233 Spring St, New York, NY 10013, USA (see also Biophysics).
The news correspondents report that additional information may be obtained from M.C. Patra, Natl Dairy Res Inst, Anim Genom Lab, Anim Biotechnol Center, Karnal 132001, Haryana, India. Additional authors for this research include S.N. Rath, S.K. Pradhan, J. Maharana and S. De.
Keywords for this news article include: Asia, India, Haryana, Biophysics, Molecular Dynamics
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