Themed collection Enzymes and Proteins

Effect of specifically located hydroxyl group in counter-acting effect of pyrophosphate anion co-product in steering carbocation migration towards itself (e.g. by further cyclization, as shown).

Factors limiting the exploitation of cytochrome P450s and significant steps which have been taken towards addressing these limitations are discussed.

Enantiomerically pure benzopyrano[3,4-b][1,4]oxazines show significant differences in their inhibitory potency of P-glycoprotein. Docking studies provide first insights into potential binding sites for these compounds.

Asymmetric carbonyl reduction using a new Clostridium acetobutylicum ADH provides access to diverse value-added chiral building blocks using biorenewable redox equivalents.

Analogues of Val and Leu having a chloro substituent in place of a methyl group are efficiently incorporated into protein.

Quantum chemistry calculations reveal that the isomer specificity of enzymes that break down hexachlorocyclohexane is constrained by the intrinsic substrate reactivity.

Modern methods ease the use and enhance the versatility of an historical protein-fragment complementation system.

Several single and double mutants from a minimal cytochrome P450 BM3 library were found to effectively oxidize cyclic and acyclic alkanes. For example, the F87A/A328V mutant hydroxylates cyclododecane to cyclododecanol.

A combination of enzymatic synthesis and click chemistry is employed for the production of starch derivatives under mild, aqueous reaction conditions.

A fast and sensitive method for screening transaminase activity and enantioselectivity, using D- and L-amino acid oxidases, allows new amine substrates to be rapidly identified.

A mechanistic insight into a phosphatase-driven supramolecular transformation whereby a peptide amphiphile switches from micellar structure to a chiral nanofibre morphology.

Tri-functional activity-based proteasome probes are used for a three-step chemical proteomics approach, in which proteasomal catalytic sites are covalently and irreversibly modified, followed by photocrosslinking of these to flanking subunits and Staudinger–Bertozzi ligation for visualization and identification of the resulting conjugates.

A photolabile linker is described for light-mediated removal of leader peptides involved in biosynthesis of posttranslationally modified peptide natural products.

An aldehyde-containing substrate for protein farnesyltransferase was shown to be enzymatically incorporated into a protein. The protein was subsequently immobilized onto aminooxy-functionalized agarose beads or labeled with a fluorophore. This method provides an alternative to the commonly employed Cu(I)-catalyzed click reaction.

Reaction strategies for employing two complementary alkene reductase enzymes in laboratory-scale conversions have been developed.

Mutants of Bacillus subtilis lipase evolved for enhanced thermostability also show increased stability in organic solvents such as acetonitrile (ACN).

MhyADH catalyses the Michael addition of water and also the subsequent oxidation to a diketone. In the absence of an oxidation reagent the reaction stops after the Michael addition.

A concept of tandem driven dynamic enzyme self-inhibition is demonstrated for acetylcholinesterase through the action of dynamic stealth inhibitors using reversible transthiolesterification.

We validate a practical methodology for the rapid profiling of small molecule inhibitors of protein–protein interactions. We find that a well known BH3 family inhibitor can potently inhibit the p53/hDM2 interaction.

I₁–Cu(II) inhibits hIAPP cytotoxicity by interfering with aggregation and cleavage.

Employing orthogonal reaction conditions an iridium catalysed oxidative hydrogen transfer was successfully coupled concurrently to an asymmetric enzyme catalysed reduction.

Variants of the N-oxygenase AurF from Streptomyces thioluteus selectively transform guanidyl- and amidinyl-substituted anilines into the corresponding nitro compounds. Site-directed mutagenesis and structural data provide new insights into regioselective N-oxygenation.

A novel preparation of sodium [¹⁸F]-fluoroacetate is described by a fluorinase catalysed reaction of S-adenosyl-L-methionine 1 with no carrier added [¹⁸F]-fluoride and then the [¹⁸F]-2 product is oxidized to [¹⁸F]-fluoroacetate by a Kuhn–Roth oxidative degradation.

The display of two sulfotyrosine residues in the α-helical fold of CCR5 can be mimicked in a β-hairpin peptidomimetic.

Peptidic ligands (16mer macrocycles) were dimerized with different geometries programmed by hybridization to recapitulate the interaction of TRAIL.

A series of analogs of dehydrophos were prepared and tested for their antimicrobial activity.

A fluopol-ABPP HTS assay identifies streptonigrin as a potent and selective PAD4 inactivator.

Data are presented that show PqqD interacting with PqqE.

The first structures of the widely-used alcohol dehydrogenase ADH-‘A’ provide new avenues for the structure-guided engineering of this useful enzyme.

The unfavourable equilibrium in a transamination with isopropylamine is displaced in an enzymatic cascade reaction using alcohol dehydrogenase in situ.

Asymmetric total synthesis of (S)-Rivastigmine was achieved via stereoselective biocatalytic transamination of acetophenone derivatives.

Catalytic activity and enantioselectivity of lipase toward poor substrates bearing bulky substituents on both sides have been dramatically improved by rational design; the E value was increased from 5 (wild-type enzyme) to >200 (I287F/I290A double mutant) with an acceleration of the reaction rate.

The first example of directed evolution of a novel P450pyr monooxygenase with inverted enantioselectivity has been demonstrated.

A silver catalyzed and microwave assisted one-pot cascade synthesis provides efficient access to diverse alkaloid-inspired scaffold classes, and a concise and efficient total synthesis of homofascaplysin C and fascaplysin.

A strategy has been demonstrated that utilizes a phosphatase as a natural tool for the triggering and control of amyloid formation in a coiled coil peptide model under conditions that closely approximate a physiological environment.

By replacing the phosphate group in pTyr with an isoxazole carboxylic acid, a novel unnatural amino acid has been successfully synthesized. Subsequently, its incorporation into a known PPI (protein–protein interaction) inhibitor of STAT3 protein (ISS 610) generated I2 which showed reasonable anti-STAT3 activity in both fluorescence polarization and cell-proliferation experiments.

The Ahp cyclodepsipeptide Symplocamide A was synthesized on solid phase, using an unsaturated amino acid as a key building block for the formation of the central Ahp moiety.

Near quantitative yields of alpha-xyloside products were obtained by coupling alpha-xylosyl fluoride with sugar acceptors using the acid/base mutant D482A of the GH31 alpha-xylosidase Yic-I

Rosetta design software was employed to remodel the substrate specificity of Drosophila melanogaster 2′-deoxyribonucleoside kinase for efficient phosphorylation of the nucleoside analog prodrug 3′-deoxythymidine.

Direct fluorescence screening of a peptide library on a SPOT array identified oligohistidines as potent esterase peptides for the hydrolysis of acetoxypyrene trisulfonates.

Characterization on xenobiotic reductase A and its mutants for enzyme functionality and stability.

The protein enantiomers D- and L-proinsulin have been prepared by total synthesis using native chemical ligation.

The first X-ray structure of kaliotoxin, enabled by ‘one pot’ chemical ligation of synthetic peptides and racemic protein crystallography.

We report a technique to visualize toxic dinoflagellates and suggest a preventative tool to warn of an impending danger and ensure the safe delivery of shellfish to the consumer market.

Phage display selection of disulfide stabilized miniproteins identified Estrogen Receptor binders displaying an LXXLL motif on a short peptide helix.

An engineered tyrosine aminomutase with high enantioselectivity was constructed by homology-modelling based mutagenesis of the active site of phenylalanine aminomutase.