Coevolution of RNA and protein subunits in RNase P and RNase MRP, two RNA processing enzymes.

RNase P and RNase mitochondrial RNA processing (MRP) are ribonucleoproteins (RNPs) that consist of a catalytic RNA and a varying number of protein cofactors. RNase P is responsible for precursor tRNA maturation in all three domains of life, while RNase MRP, exclusive to eukaryotes, primarily functions in rRNA biogenesis. While eukaryotic RNase P is associated with more protein cofactors and has an RNA subunit with fewer auxiliary structural elements compared to its bacterial cousin, the double-anchor precursor tRNA recognition mechanism has remarkably been preserved during evolution. RNase MRP shares evolutionary and structural similarities with RNase P, preserving the catalytic core within the RNA moiety inherited from their common ancestor. By incorporating new protein cofactors and RNA elements, RNase MRP has established itself as a distinct RNP capable of processing ssRNA substrates. The structural information on RNase P and MRP helps build an evolutionary trajectory, depicting how emerging protein cofactors harmonize with the evolution of RNA to shape different functions for RNase P and MRP. Here, we outline the structural and functional relationship between RNase P and MRP to illustrate the coevolution of RNA and protein cofactors, a key driver for the extant, diverse RNP world.

Unveiling Nonsecular Collisional Dissipation of Molecular Alignment.

We conducted a joint theoretical and experimental study to investigate the collisional dissipation of molecular alignment. By comparing experimental measurements to the quantum simulations, the nonsecular effect in the collision dissipation of molecular alignment was unveiled from the gas-density-dependent decay rates of the molecular alignment revival signals. Different from the conventional perspective that the nonsecular collisional effect rapidly fades within the initial few picoseconds following laser excitation, our simulations of the time-dependent decoherence process demonstrated that this effect can last for tens of picoseconds in the low-pressure regime. This extended timescale allows for the distinct identification of the nonsecular effect from molecular alignment signals. Our findings present the pioneering evidence that nonsecular molecular collisional dissipation can endure over an extended temporal span, challenging established concepts and strengthening our understanding of molecular dynamics within dissipative environments.

Ultrafast Picometer-Resolved Molecular Structure Imaging by Laser-Induced High-Order Harmonics.

Real-time visualization of molecular transformations is a captivating yet challenging frontier of ultrafast optical science and physical chemistry. While ultrafast x-ray and electron diffraction methods can achieve the needed subangstrom spatial resolution, their temporal resolution is still limited to hundreds of femtoseconds, much longer than the few femtoseconds required to probe real-time molecular dynamics. Here, we show that high-order harmonics generated by intense femtosecond lasers can be used to image molecules with few-ten-attosecond temporal resolution and few-picometer spatial resolution. This is achieved by exploiting the sensitive dependence of molecular recombination dipole moment to the geometry of the molecule at the time of harmonic emission. In a proof-of-principle experiment, we have applied this high-harmonic structure imaging (HHSI) method to monitor the structural rearrangement in NH_{3}, ND_{3}, and N_{2} from one to a few femtoseconds after the molecule is ionized by an intense laser. Our findings establish HHSI as an effective approach to resolve molecular dynamics with unprecedented spatiotemporal resolution, which can be extended to trace photochemical reactions in the future.

Computational simulations uncover enantioselective metabolism of chiral triazole fungicides by human CYP450 enzymes: A case study of tebuconazole.

Tebuconazole (TEB), a prominent chiral triazole fungicide, has been extensively utilized for plant pathogen control globally. Despite experimental evidence of TEB metabolism in mammals, the enantioselectivity in the biotransformation of R- and S-TEB enantiomers by specific CYP450s remains elusive. In this work, integrated in silico simulations were employed to unveil the binding interactions and enantioselective metabolic fate of TEB enantiomers within human CYP1A2, 2B6, 2E1, and 3A4. Molecular dynamics (MD) simulations clearly delineated the binding specificity of R- and S-TEB to the four CYP450s, crucially determining their differences in metabolic activity and enantioselectivity. The primary driving force for robust ligand binding was identified as van der Waals interactions with CYP450s, particularly involving the hydrophobic residues. Mechanistic insights derived from quantum mechanics/molecular mechanics (QM/MM) calculations established C2-methyl hydroxylation as the predominant route of R-/S-TEB metabolism, while C6-hydroxylation and triazol epoxidation were deemed kinetically infeasible pathways. Specifically, the resulting hydroxy-R-TEB metabolite primarily originates from R-TEB biotransformation by 1A2, 2E1 and 3A4, whereas hydroxy-S-TEB is preferentially produced by 2B6. These findings significantly contribute to our comprehension of the binding specificity and enantioselective metabolic fate of chiral TEB by CYP450s, potentially informing further research on human health risk assessment associated with TEB exposure.