Ultrafast dynamics of an azobenzene-containing molecular shuttle based on a rotaxane

An ultrafast spectroscopic study was carried out for a photoisomerizable, rotaxane-based molecular shuttle, in which photoisomerization of the azobenzene moiety of the thread-like guest drives a shuttling motion of a...

Regulation of the Molecular Shuttle Service: A Multiscale Model of Aquaporin 2 Recycling

The response of cells to their environment is driven by a variety of proteins and messenger molecules. In eukaryotes their distribution, which is regulated by a vesicular transport system, is important for a tight cellular response. The recycling of aquaporin 2 between membrane and storage region is a crucial part of the body water homeostasis and its malfunction can lead to Diabetes insipidus. To understand the regulation of this system, we aggregated pathways and mechanisms from literature and derived three models in a hypothesis-driven approach. Furthermore, we combined the models to a single system to gain insight into key regulatory mechanisms. To achieve this we developed a multiscale computational framework for the modeling and simulation of cellular systems. The analysis of the system rationalises that the compartmentalization of cAMP in renal principal cells is a result of the protein kinase A signalosome and can only occur if specific cellular components are observed in conjunction. Endocytotic and exocytotic processes are inherently connected and can be regulated by the same protein kinase A signal.

Exploring the dynamics of Zr-based metal–organic frameworks containing mechanically interlocked molecular shuttles

MOFs UiO-68 and PCN-57, containing triphenylene linkers, were doped with a tetracarboxylate linker that contains a [2]rotaxane molecular shuttle, and VT CP MAS 13C SSNMR was used to explore the motion of the macrocyclic ring inside the cavities.

Translational dynamics of a non-degenerate molecular shuttle imbedded in a zirconium metal–organic framework

An unsymmetrical molecular shuttle was incorporated into the octahedral cavities of a Zr(iv) MOF. 13C SSNMR showed that the presence of mesitylene in the pores results in an increase in the barriers for the thermally driven motion of the macrocycle.

Structure-based dynamic analysis of the glycine cleavage system suggests key residues for control of a key reaction step

Molecular shuttles play decisive roles in many multi-enzyme systems such as the glycine cleavage system (GCS) for one-carbon (C1) metabolism. In GCS, a lipoate swinging arm containing an aminomethyl moiety is attached to protein H and serves as a molecular shuttle among different proteins. Protection of the aminomethyl moiety in a cavity of protein H and its release induced by protein T are key processes but barely understood. Here, we present a detailed structure-based dynamic analysis of the induced release of the lipoate arm of protein H. Based on molecular dynamics simulations of interactions between proteins H and T, four major steps of the release process showing significantly different energy barriers and time scales can be distinguished. Mutations of a key residue, Ser-67 in protein H, led to a bidirectional tuning of the release process. This work opens ways to target C1 metabolism in biomedicine and the utilization of formate and CO2 for biosynthesis.