Enantioselective interactions of aminonitrile dimers.

Enantioenrichment of amino acids is essential during the early chemical evolution leading to the origin of life. However, the detailed molecular mechanisms remain unsolved. Dimerization of enantiomers is the first molecular process in the nucleation of deposition and crystallization, which are both essential for enantioenrichment.

Similarity between oxygen evolution in photosystem II and oxygen reduction in cytochrome c oxidase via proton coupled electron transfers. A unified view of the oxygenic life from four electron oxidation-reduction reactions.

Basic concepts and theoretical foundations of broken symmetry (BS) and post BS methods for strongly correlated electron systems (SCES) such as electron-transfer (ET) diradical, multi-center polyradicals with spin frustration are described systematically to elucidate structures, bonding and reactivity of the high-valent transition metal oxo bonds in metalloenzymes: photosystem II (PSII) and cytochrome c oxidase (CcO). BS hybrid DFT (HDFT) and DLPNO coupled-cluster (CC) SD(T) computations are performed to elucidate electronic and spin states of CaMnO cluster in the key step for oxygen evolution, namely S [S with Mn(IV) = O + Tyr161-O radical] state of PSII and P [Fe(IV) = O + HO-Cu(II) + Tyr161-O radical] step for oxygen reduction in CcO. The cycle of water oxidation catalyzed by the CaMnO cluster in PSII and the cycle of oxygen reduction catalyzed by the Cu-Fe-Fe-Cu cluster in CcO are examined on the theoretical grounds, elucidating similar concerted and/or stepwise proton transfer coupled electron transfer (PT-ET) processes for the four-electron oxidation in PSII and four-electron reduction in CcO.

Calcium Binding Mechanism in TAT Rhodopsin.

TAT rhodopsin binds Ca near the Schiff base region, which accompanies deprotonation of the Schiff base. This paper reports the Ca-free and Ca-bound structures of TAT rhodopsin by molecular dynamics (MD) simulation launched from AlphaFold structures. In the Ca-bound TAT rhodopsin, Ca is directly coordinated by eight oxygen atoms, four oxygens of the side chains of E54 and D227, and four oxygens of water molecules.

Real-time observation of a metal complex-driven reaction intermediate using a porous protein crystal and serial femtosecond crystallography.

Determining short-lived intermediate structures in chemical reactions is challenging. Although ultrafast spectroscopic methods can detect the formation of transient intermediates, real-space structures cannot be determined directly from such studies. Time-resolved serial femtosecond crystallography (TR-SFX) has recently proven to be a powerful method for capturing molecular changes in proteins on femtosecond timescales.

A new small molecule DoNA binding to CAG repeat RNA.

We here report a new molecule DoNA binding to a CAG repeat RNA. DoNA is a dimer of the NA molecule that we previously reported. NA binds with high affinity to a CAG repeat DNA but not significantly to a CAG repeat RNA.

Theoretical elucidation of the structure, bonding, and reactivity of the CaMnO clusters in the whole Kok cycle for water oxidation embedded in the oxygen evolving center of photosystem II. New molecular and quantum insights into the mechanism of the O-O bond formation.

This paper reviews our historical developments of broken-symmetry (BS) and beyond BS methods that are applicable for theoretical investigations of metalloenzymes such as OEC in PSII. The BS hybrid DFT (HDFT) calculations starting from high-resolution (HR) XRD structure in the most stable S state have been performed to elucidate structure and bonding of whole possible intermediates of the CaMnO cluster (1) in the S (i = 0 ~ 4) states of the Kok cycle. The large-scale HDFT/MM computations starting from HR XRD have been performed to elucidate biomolecular system structures which are crucial for examination of possible water inlet and proton release pathways for water oxidation in OEC of PSII.

Origin of Homochirality in Amino Acids Induced by Lyman-α Irradiation in the Early Stage of the Milky Way.

The enantiomeric excess (ee) of l-form amino acids found in the Murchison meteorite poses some issues about the cosmic origin of their chirality. Circular dichroism (CD) spectra of amino acids in the far-ultraviolet (FUV) at around 6.8 eV (182 nm) indicate that the circularly polarized light can induce ee through photochemical reactions.

Enantiomeric Excesses of Aminonitrile Precursors Determine the Homochirality of Amino Acids.

High enantiomeric excesses (ee's) of l-amino acids, including non-proteinogenic amino acid isovaline (Iva), were discovered in the Murchison meteorite, but the detailed molecular mechanism responsible for the observed ee of amino acids remains elusive and inconsistent, because Iva has an inverted circular dichroism (CD) spectrum with respect to α-H amino acids, e.g., alanine.

Specific zinc binding to heliorhodopsin.

Heliorhodopsins (HeRs), a recently discovered family of rhodopsins, have an inverted membrane topology compared to animal and microbial rhodopsins. The slow photocycle of HeRs suggests a light-sensor function, although the actual function remains unknown. Although HeRs exhibit no specific binding of monovalent cations or anions, recent ATR-FTIR spectroscopy studies have demonstrated the binding of Zn to HeR from archaeon (TaHeR) and 48C12.

Roles of the Flexible Primary Coordination Sphere of the MnCaO Cluster: What Are the Immediate Decay Products of the State?

The primary coordination sphere of the multinuclear cofactor (MnCaO) in the oxygen-evolving complex (OEC) of photosystem II is absolutely conserved to maintain its structure and function. Recent time-resolved serial femtosecond crystallography identified large reorganization of the primary coordination sphere in the to transition, which elicits a cascade of events involving Mn oxidation and water molecule binding to a putative catalytic Mn site. We examined how the crystallographic fields, created by transient conformational states of the OEC at various time points, affect the thermodynamics of various isomers of the Mn cluster using DFT calculations, with an aim of comprehending the functional roles of the flexible primary coordination sphere in the to transition and in the recovery of the state.

Estimation of the relative contributions to the electronic energy transfer rates based on Förster theory: The case of C-phycocyanin chromophores.

In the present study, we provide a reformulation of the theory originally proposed by Förster which allows for simple and convenient formulas useful to estimate the relative contributions of transition dipole moments of a donor and acceptor (chemical factors), their orientation factors (intermolecular structural factors), intermolecular center-to-center distances (intermolecular structural factors), spectral overlaps of absorption and emission spectra (photophysical factors), and refractive index (material factor) to the excitation energy transfer (EET) rate constant. To benchmark their validity, we focused on the EET occurring in C-phycocyanin (C-PC) chromophores. To this aim, we resorted to quantum chemistry calculations to get optimized molecular structures of the C-PC chromophores within the density functional theory (DFT) framework.

pyProGA-A PyMOL plugin for protein residue network analysis.

The field of protein residue network (PRN) research has brought several useful methods and techniques for structural analysis of proteins and protein complexes. Many of these are ripe and ready to be used by the proteomics community outside of the PRN specialists. In this paper we present software which collects an ensemble of (network) methods tailored towards the analysis of protein-protein interactions (PPI) and/or interactions of proteins with ligands of other type, e.

Weak O binding and strong HO binding at the non-heme diiron center of trypanosome alternative oxidase.

Alternative oxidase (AOX) catalyzes the four-electron reduction of dioxygen to water as an additional terminal oxidase, and the catalytic reaction is critical for the parasite to survive in its bloodstream form. Recently, the X-ray crystal structure of trypanosome alternative oxidase (TAO) complexed with ferulenol was reported and the molecular structure of the non-heme diiron center was determined. The binding of O was a unique side-on type compared to other iron proteins.

Unique protonation states of aspartate and topaquinone in the active site of copper amine oxidase.

The oxidative deamination of biogenic amines, crucial in the metabolism of a wealth of living organisms, is catalyzed by copper amine oxidases (CAOs). In this work, on the ground of accurate molecular modeling, we provide a clear insight into the unique protonation states of the key catalytic aspartate residue Asp298 and the prosthetic group of topaquinone (TPQ) in the CAO of (AGAO). This provides both extensions and complementary information to the crystal structure determined by our recent neutron diffraction (ND) experiment.

Reaction mechanism of N-cyclopropylglycine oxidation by monomeric sarcosine oxidase.

Monomeric sarcosine oxidase (MSOX) is a fundamental - yet one of the simplest - member of a family of flavoenzymes able to catalyze the oxidation of sarcosine (N-methylglycine) and other secondary amines. MSOX is one of the best characterized members of the amine oxidoreductases (AOs), however, its reaction mechanism is still controversial. A single electron transfer (SET) process was suggested on the basis of studies with N-cyclopropylglycine (CPG), although a hydride transfer mechanism would be more consistent in general for AOs.

Neutron crystallography of copper amine oxidase reveals keto/enolate interconversion of the quinone cofactor and unusual proton sharing.

Recent advances in neutron crystallographic studies have provided structural bases for quantum behaviors of protons observed in enzymatic reactions. Thus, we resolved the neutron crystal structure of a bacterial copper (Cu) amine oxidase (CAO), which contains a prosthetic Cu ion and a protein-derived redox cofactor, topa quinone (TPQ). We solved hitherto unknown structures of the active site, including a keto/enolate equilibrium of the cofactor with a nonplanar quinone ring, unusual proton sharing between the cofactor and the catalytic base, and metal-induced deprotonation of a histidine residue that coordinates to the Cu.

Reaction of threonine synthase with the substrate analogue 2-amino-5-phosphonopentanoate: implications into the proton transfer at the active site.

Threonine synthase catalyses the conversion of O-phospho-l-homoserine and a water molecule to l-threonine and has the most complex catalytic mechanism among the pyridoxal 5'-phosphate-dependent enzymes. In order to study the less-characterized earlier stage of the catalytic reaction, we studied the reaction of threonine synthase with 2-amino-5-phosphonopentanoate, which stops the catalytic reaction at the enamine intermediate. The global kinetic analysis of the triphasic spectral changes showed that, in addition to the theoretically expected pathway, the carbanion is rapidly reprotonated at Cα to form an aldimine distinct from the external aldimine directly formed from the Michaelis complex.