Biology subjects

Lee, O.-S.

Publications and source records attributed to Lee, O.-S..

2 recordsLinked to original sources

bioRxiv2024

Computational Insights into the molecular dynamics of the binding of ligands in the Methanol Dehydrogenase

Methanol dehydrogenase (MDH) is a promising biocatalyst for industrial use, converting methanol to formaldehyde. Our molecular modeling revealed methanol binds to MDH with [~]7 kcal/mol free energy, while formaldehyde binds with [~]4 kcal/mol. This suggests methanol remains longer in the active site, and formaldehyde exits more readily post-reaction. These insights are crucial for designing more efficient MDH variants for industrial applications. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/602606v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@442a65org.highwire.dtl.DTLVardef@13b877eorg.highwire.dtl.DTLVardef@13c8ef6org.highwire.dtl.DTLVardef@cde32b_HPS_FORMAT_FIGEXP M_FIG C_FIG The left panel shows methanol and formaldehyde within the active site of methanol dehydrogenase, illustrating entry and release paths. The right panel presents the free energy profiles, indicating methanols stronger binding affinity and formaldehydes easier release post-reaction.

biophysics↗

bioRxiv2023

PIP2 electrostatically triggers vesicle fusion: arresting full SNARE assembly and vesicle fusion by PIP2-masking

SNARE proteins drive vesicle fusion and neurotransmitters release. Given that exocytosis is fast, and vesicle docking is tight, SNARE proteins are likely pre-assembled before fusion. However, the molecular mechanisms of the partially-assembled SNARE complex remain controversial. We use amperometry and the reconstitution of native vesicle fusion to show that MARCKS arrests basal fusion by masking PIP2 in a vesicle docking state where the SNARE complex is partially assembled. Ca2+/CaM or PKC-epsilon unmask PIP2 through the MARCKS dissociation, and thus rescue basal fusion and potentiates synaptotagmin-1-mediated Ca2+-dependent vesicle fusion. Our data provide the novel model that PIP2 electrostatically triggers vesicle fusion by lowering the hydration energy, and that masking PIP2 arrests vesicle fusion in a state of the partial SNARE assembly. Vesicle-mimicking liposomes fail to arrest vesicle fusion by masking PIP2, indicating that native vesicles are essential for the reconstitution of physiological vesicle fusion. One Sentence SummaryMasking PIP2 by MARCKS arrests the full SNARE assembly and vesicle fusion.

neuroscience↗