Enzymatic stereodivergent synthesis to access all possible product stereoisomers bearing multiple stereocenters is relatively undeveloped, although enzymes are being increasingly used in both academic and industrial areas. When two thus four stereoisomeric products involved, obtaining enzyme mutants for individually accessing would be ideal. Although significant success has been achieved directed evolution of general, engineering one into highly stereocomplementary variants the full...

Abstract Engineering artificial enzymes with high activity and catalytic mechanism different from naturally occurring is a challenge in protein design. For example, many attempts have been made to obtain active hydrolases by introducing Ser → Cys exchange at the respective triads, but this generally induced breakdown of activity. We now report that long-standing dogma no longer pertains, provided additional mutations are introduced directed evolution. By employing Candida antarctica lipase B...

Aziridines are present in many synthetic pharmaceuticals. The synthesis of aziridine ring remains challenging due to its highly strained three-membered structure. Recently, a non-heme αKG-dependent enzyme TqaL have been...

Abstract Heme d1, a vital tetrapyrrol involved in the denitrification processes is synthesized from its precursor molecule precorrin-2 chemical reaction catalysed by an S-adenosyl-L-methionine (SAM) dependent Methyltransferase (NirE). The NirE enzyme catalyses transfer of methyl group SAM to uroporphyrinogen III and serves as novel potential drug target for pharmaceutical industry. An important insight into structure-activity relationships has been revealed elucidating crystal structure, but...

Abstract The gut bacterial bile salt hydrolase (BSH) plays a critical role in host lipid metabolism and energy harvest. Therefore, BSH is promising microbiome target to develop new therapies regulate obesity humans novel non-antibiotic growth promoters for food animals. We previously reported the 1.90 Å apo crystal structure of from Lactobacillus salivarius ( ls BSH). In this study, we soaked with glycocholic acid (GCA), substrate, obtained 2.10 containing complex bound GCA cholic (CA),...

Electron/proton transfers in water proceeding from ground/excited states are the elementary reactions of chemistry. These an iconic class molecules─polypyridineRu(II)─are now controlled by capturing or releasing three them with hosts that shape-switchable. Reversible erection collapse host walls allows such switchability. Some reaction rates suppressed factors up to 120 inclusive binding metal complexes. This puts nanometric coordination chemistry a box can be open shut as necessary. Such...

Terpene synthases (TPS) catalyze the cyclization of acyclic prenyl diphosphate precursor and are responsible for abundance natural product terpene in nature. The biosynthesis terpenoid by nonseed plant TPS is not well understood due to highly dynamic feature reaction unavailability enzyme structure. Here we discovered a class I JeST4 from Jungermannia exsertifolia elucidated its catalytically active structure complex with substrate key carbocation intermediates during catalysis. We found...

Collagenolysis is catalyzed by enzymes from the matrix metalloproteinase (MMP) family, where one of most studied MMP-1.

The selective oxidation of C–H in artemisinin by P450_BM3 variants was disclosed combining QM/MM and MD simulations.

Alkylguaiacols are lignin-derived products obtained by reductive catalytic fractionation (RCF) of lignocellulosic biomass.

Matrix metalloproteinase-1 (MMP-1) is one of the most widely studied enzymes involved in collagen degradation. Mutations specific residues MMP-1 hemopexin-like (HPX) domain have been shown to modulate activity catalytic (CAT) domain. In order reveal structural and conformational effects such mutations, a molecular dynamics (MD) study was performed silico mutated X-ray crystallographic structure complexed with collagen-model triple-helical peptide (THP). The results indicate an important role...

The selective α,β-desaturation of cyclic carbonyl compounds, which are found in the core many steroid and bioactive molecules, using green chemistry is highly desirable. To achieve this task, we have for first time described solved de novo structure a member cyclohexanone dehydrogenase class enzymes. breadth substrate specificity was investigated by assaying dehydrogenase, from Alicycliphilus denitrificans, against several ketones, lactones lactams. investigate binding, catalytic variant,...

Lipoproteins are essential for bacterial survival. Bacterial lipoprotein biosynthesis is accomplished by sequential modification three enzymes in the inner membrane, all of which emerging antimicrobial targets. The X-ray crystal structure prolipoprotein diacylglyceryl transferase (Lgt) and apolipoprotein N-acyl (Lnt) has been reported. However, mechanisms post-translational catalyzed these have not understood. Here, we studied mechanism transacylation reaction Lgt, first enzyme using...

Histone demethylases (KDMs) catalyze histone lysine demethylation, an important epigenetic process that controls gene expression in eukaryotes, and represent cancer drug targets for treatment. Demethylation of is comprised sequential reaction steps including oxygen activation, decarboxylation, demethylation. The initial binding activation have been studied. However, the information on complete catalytic cycle limited, which has impeded structure-based design inhibitors targeting KDMs. Here...

Cytochrome P450GcoA is an enzyme that catalyzes the guaiacol unit of lignin during breakdown via aryl-O-demethylation reaction. This reaction intriguing and commercial importance for its potential applications in production biofuel plastic from biomass feedstock. Recently, F169A mutation elicits a promiscuous activity syringol while maintaining native guaiacol. Using comprehensive MD simulations hybrid QM/MM calculations, we address, herein, origin promiscuity relevance to specific toward...

Isopentenyl phosphate kinase (IPK) catalyzes the Mg2+-ATP dependent phosphorylation reactions to produce isopentenyl diphosphate, an important precursor in synthesis of isopentenols. However, position divalent metal ion crystal structures IPK complex with ATP and its native substrate IP has not been definitively resolved, as a result ambiguity surrounds catalytic mechanism IP, limiting exploitation biofuel drug design. Here we report catalytically competent structure Mg2+ elucidate reaction...

Abstract Lipoproteins serve diverse functions in the bacterial cell and some are essential for survival. Some lipoproteins adjuvants eliciting responses from innate immune system of host. The growing list membrane enzymes responsible lipoprotein synthesis includes recently discovered intramolecular transacylase, Lit. Lit creates a that is less immunogenic, possibly enabling bacteria to gain foothold host by stealth. Here, we report crystal structure enzyme Bacillus cereus describe its...

Conformational flexibility influence the binding of substrate and cofactor in TPST-2.

A recently discovered heme-dependent enzyme tyrosine hydroxylase (TyrH) offers a green approach for functionalizing the high-strength C–H and C–F bonds in aromatic compounds. However, there is ambiguity regarding nature of oxidant (compound 0 or compound I) involved activating these bonds. Herein, using comprehensive molecular dynamics (MD) simulations hybrid quantum mechanical/molecular mechanical calculations, we reveal that it I (Cpd acts as primary functionalization both The energy...

The dynamics of the loop controls promiscuous activity in HisA enzyme.

Tyrosylprotein sulfotransferase-2 catalyses important, but a less explored posttranslational modification of proteins.

Two homologous 2-oxoglutarate-dependent (ODD) nonheme enzymes thebaine 6-O-demethylase (T6ODM) and codeine-3-O-demethylase (CODM), are involved in the morphine biosynthesis pathway from thebaine, catalyzing O-demethylation reaction with precise regioselectivity at C6 C3 positions of respectively. We investigated origin these by combined molecular dynamics (MD) quantum mechanics/molecular mechanics (QM/MM) calculations found that Thebaine binds two distinct sites T6ODM CODM, which determines...

Lignin, a complex plant cell wall component, holds promise as renewable aromatic carbon feedstock. p-Vanillin is key product of lignin depolymerization and precursor protocatechuic acid (PCA) that has tremendous potential for biofuel production. While the GcoAB enzyme, native to Amycolatopsis sp., naturally catalyzes aryl-O-demethylation toward guaiacol, recent research introduced single mutation, T296S, into GcoA P450 enabling it catalyze p-vanillin. This structural modification increases...

A recurring dream of molecular recognition is to create receptors that distinguish between closely related targets with sufficient accuracy, especially in water. The more useful the targets, valuable becomes. We now present multianionic trimeric cyclophane a remarkable ability bind iconic (bipyridine)3Ru(II) (with its huge range applications) while rejecting nearly equally (phenanthroline)3Ru(II). These not only selectively capture but also can be redox-switched release guest. 1D- and...

Staurosporine (STU) is a microbial alkaloid which an universal kinase inhibitor. In order to understand its mechanism of action it important explore structure-properties relationships. this paper we provide the results computational study structure, chiroptical properties, conformational flexibility STU as well correlation between electronic circular dichroism (ECD) spectra and structure complex with anaplastic lymphoma kinase.