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Structural and chemical biology

This collection highlights a selection of recent studies published in Communications Chemistry relating to the structure, function, and chemical modification of biomolecules. The Biocatalysis section features articles which probe mechanisms of enzyme activity, or engineer enzymes for new synthetic applications. The Computational Structural Biology section encompasses new insights into the structure and function of enzymes from modern computational chemistry. And under Bioconjugation we showcase tools for the study of biological function, including bioorthogonal labeling methods and environmentally responsive fluorescent probes.

These articles have been collated by Prof. Akane Kawamura, Editorial Board Member for Communications Chemistry, and Dr Andrew Bissette, Senior Editor.

Biocatalysis

Hypoxia-inducible factor (FIH) is an oxygenase which post-translationally hydroxylates proteins and is implicated in a range of biological processes. Here a wide substrate tolerance for FIH is demonstrated, including for d-amino acids, where double hydroxylation of d-leucine is observed.

Article | Open Access | | Communications Chemistry

Beta-lactams are important antiobiotics but synthesising functionalised derivatives in high enantiomeric purity can be challenging. Here malonyl-CoA derivatives are applied in an enantioselective multi-enzyme cascade, yielding beta-lactams bearing three contiguous chiral centres in high diastereomeric purity.

Article | Open Access | | Communications Chemistry

Regioselective methods for the reversible formation and breakage of C-O-ether bonds under mild conditions are desired. Here, the authors present a biocatalytic shuttle concept using corrinoid-dependent methyl transferases for demethylating various phenyl methyl ethers and functionalizing substituted catechols.

Article | Open Access | | Communications Chemistry

Computational structural biology

The relationship between molecular motion and catalysis in enzymes is debated. Here, simulations of cyclophilin A and three catalytically-impaired mutants reveal a nanosecond-scale interconversion between active and inactive conformations, orders of magnitude faster than previously suggested.

Article | Open Access | | Communications Chemistry

Displacement of water molecules from proteins can lead to higher affinity or selectivity of ligands, but measuring individual water binding energies is challenging. Here calculated binding free energies are used to estimate the stability of conserved water in 35 bromodomains and to predict the ease of displacement.

Article | Open Access | | Communications Chemistry

Bioconjugation

Strained alkenes are valuable reagents for rapid and selective labeling of biomolecules but may undergo side-reactions. Here direct excitation of an azobenzene generates a strained nitrogen-nitrogen double bond in situ which reacts with a photochemically-generated nitrile imine, allowing the labeling of live cells with spatiotemporal control.

Article | Open Access | | Communications Chemistry

Ligand-directed protein labeling allows selective modification of native proteins but typically requires stoichiometric quantities of the labeling agent. Here a substoichiometric quantity of a peptide probe bound to a photocatalyst allows selective labeling of a target protein Cys residue in the presence of structurally similar proteins.

Article | Open Access | | Communications Chemistry

Oligomerisation is widely used to engineer proteins and peptides with desirable properties. Here, covalent homodimers and heterodimers of fluorescent proteins are designed in silico and experimentally shown to exhibit differing spectral properties depending upon the structure of the protein-protein interface.

Article | Open Access | | Communications Chemistry

Phenol and cyclohexenone can interconvert by controlled palladium-catalyzed hydrogenation or oxidation, allowing N-functionalization of amines. Here this is applied to amino acids and small peptides, allowing a range of challenging substrates to be N-arylated using cyclohexenone or N-alkylated using phenol.

Article | Open Access | | Communications Chemistry