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Nature Chemical Biology Contents: July 2017, Volume 13 No 7 pp 693 - 813

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Nature Chemical Biology

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July 2017 Volume 13, Issue 7

Research Highlights
News and Views
Brief Communication

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Research Highlights


Metal homeostasis: Pumping iron | Antimicrobials: Targeting fungal chromatin | Synthetic biology: Playing favorites | Circadian regulation: Switching periods

News and Views


Antibiotic resistance: Blocking tetracycline destruction   pp694 - 695
Sonja Petkovic and Winfried Hinrichs
Enzymology and structural and functional characterization of some FAD-dependent monooxygenases provide insights into degradation of tetracycline antibiotics, but also show unexpected features of substrate recognition, reaction mechanism, and competitive inhibition.

See also: Article by Park et al.

Peptidoglycan: Another brick in the wall   pp695 - 696
Anthony J Clarke
Lipid II embodies the bricks used to build the essential bacterial cell wall component peptidoglycan. A facile new procedure for preparation of species-specific Lipid II in high yields can now be used to unlock the door to antibiotic discovery.

See also: Article by Qiao et al.

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Targeting the N terminus for site-selective protein modification   pp697 - 705
Christian B Rosen and Matthew B Francis

A variety of chemical and enzymatic techniques, each with their own considerations for use, have been developed for the site-selective bioconjugation of desirable moieties to proteins via the unique handle of the N terminus.

Brief Communication


Engineering RGB color vision into Escherichia coli   pp706 - 708
Jesus Fernandez-Rodriguez, Felix Moser, Miryoung Song and Christopher A Voigt

A synthetic biology system composed of light-wavelength-responsive genetic regulators, signal-processing circuits and pigment-production pathways have resulted in an Escherichia coli strain that can record color images in RGB format.



Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases   pp709 - 714
Linda Lauinger, Jing Li, Anton Shostak, Ibrahim Avi Cemel, Nati Ha et al.

The bicyclic disulfide-containing compound thiolutin has broad antimicrobial activity and targets the essential proteasomal deubiquitinase Rpn11 and other metalloproteases, leading to inhibition of enzymatic activity through a mechanism involving zinc chelation.
Chemical compounds

Computational design of ligand-binding membrane receptors with high selectivity   pp715 - 723
Xiang Feng, Joaquin Ambia, Kuang-Yui M Chen, Melvin Young and Patrick Barth

An integrated homology modeling and docking strategy, IPHoLD, is used to predict protein-ligand binding sites and poses, allowing blind prediction of GPCR-ligand conformations and design of dopamine receptors with novel ligand-binding selectivity.

Membrane curvature regulates ligand-specific membrane sorting of GPCRs in living cells   pp724 - 729
Kadla R Rosholm, Natascha Leijnse, Anna Mantsiou, Vadym Tkach, Soren L Pedersen et al.

Membrane curvature induces sorting of GPCRs within live-cell-membrane protrusions, and the curvature-dependent sorting is affected by agonist binding. Thermodynamic modeling suggests that this is due to an energetic drive to match receptor shape and elasticity to membrane curvature.

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes   pp730 - 736
Jooyoung Park, Andrew J Gasparrini, Margaret R Reck, Chanez T Symister, Jennifer L Elliott et al.

Structural and functional characterization of tetracycline-inactivating enzymes reveals that inhibitors act by locking the enzyme in an unproductive state by restricting substrate-driven conformational dynamics that are important for catalysis.

See also: News and Views by Petkovic & Hinrichs

β-Lactone formation during product release from a nonribosomal peptide synthetase   pp737 - 744
Jason E Schaffer, Margaret R Reck, Neha K Prasad and Timothy A Wencewicz

In vitro reconstitution of five enzymes elucidates the biosynthetic pathway of obafluorin (Obi) and reveals that ObiF uses an unusual thioesterase domain to cyclize the product to a strained β-lactone during release from the NRPS assembly line.
Chemical compounds

A conserved threonine prevents self-intoxication of enoyl-thioester reductases   pp745 - 749
Raoul G Rosenthal, Bastian Vogeli, Tristan Wagner, Seigo Shima and Tobias J Erb

A conserved threonine in medium-chain dehydrogenases/reductases is essential to suppress the formation of an inhibitory side product, which suggests that it functions to destabilize competing transition states rather than to promote positive catalysis.

Developing Spindlin1 small-molecule inhibitors by using protein microarrays   pp750 - 756
Narkhyun Bae, Monica Viviano, Xiaonan Su, Jie Lv, Donghang Cheng et al.

The use of protein microarrays containing human methyllysine effector molecules enabled discovery of a potent and selective inhibitor of the interaction of the Tudor-domain-containing protein Spindlin1 with H3K4me3.
Chemical compounds

Recognition of EGF-like domains by the Notch-modifying O-fucosyltransferase POFUT1   pp757 - 763
Zhijie Li, Kristina Han, John E Pak, Malathy Satkunarajah, Dongxia Zhou et al.

X-ray crystallographic analysis of the mouse protein-O-fucosyltransferase POFUT1 combined with average structural map analysis demonstrate that POFUT1 specifically recognizes only one of the four EGF-like domain types found in nature.

Engineering protein stability with atomic precision in a monomeric miniprotein   pp764 - 770
Emily G Baker, Christopher Williams, Kieran L Hudson, Gail J Bartlett, Jack W Heal et al.

The design and mutagenesis of an α-helix-containing monomeric miniprotein, PPα-Tyr, provide insights into weak noncovalent CH-π interactions that help define and stabilize folded proteins and protein-ligand interactions.

A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor   pp771 - 778
Marco P Licciardello, Anna Ringler, Patrick Markt, Freya Klepsch, Charles-Hugues Lardeau et al.

The use of a refined chemical library called the CeMM library of unique drugs (CLOUD) identified a synergistic interaction between flutamide and phenprocoumon in decreasing the growth of prostate cancer cells by regulating androgen receptor stability.

Structural and functional characterization of the hydrogenase-maturation HydF protein   pp779 - 784
Giorgio Caserta, Ludovic Pecqueur, Agnieszka Adamska-Venkatesh, Cecilia Papini, Souvik Roy et al.

The structure of the hydrogenase-maturation protein HydF in the holo form with its [4Fe-4S] cluster reveals a labile glutamate ligand that allows binding of artificial 2Fe subcluster mimics, thus endowing HydF with its own hydrogenase activity.
Chemical compounds

Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A   pp785 - 792
Casey L Quinlan, Stephen E Kaiser, Ben Bolanos, Dawn Nowlin, Rita Grantner et al.

PF-9366 inhibits Mat2A by binding to an allosteric site that overlaps with the binding site of Mat2B, altering the active site and supporting a model in which Mat2B can be either an inhibitor or an activator of Mat2A, depending on methionine and SAM levels.
Chemical compounds

Lipid II overproduction allows direct assay of transpeptidase inhibition by β-lactams   pp793 - 798
Yuan Qiao, Veerasak Srisuknimit, Frederick Rubino, Kaitlin Schaefer, Natividad Ruiz et al.

The isolation of Lipid II, accumulated as a result of chemical probe treatment, enables the reconstitution of crosslinked peptidoglycan biosynthesis and a direct transpeptidase assay for PBP2 inhibition by β-lactams.

See also: News and Views by Clarke

Functional selectivity of GPCR-directed drug action through location bias   pp799 - 806
Roshanak Irannejad, Veronica Pessino, Delphine Mika, Bo Huang, Philip B Wedegaertner et al.

Intracellular Gs-cAMP signaling from β1-adrenergic receptors residing in the Golgi represents /`location bias/', a new form of GPCR functional selectivity. Inactive Golgi-localized receptors can be activated by some β1-targeting drugs.

Structural basis for high-affinity fluorophore binding and activation by RNA Mango   pp807 - 813
Robert J Trachman III, Natalia A Demeshkina, Matthew W L Lau, Shanker Shyam S Panchapakesan, Sunny C Y Jeng et al.

A crystal structure of the RNA aptamer Mango bound to a thiazole orange-derived fluorophore reveals a three-tiered G-quadruplex structure, which, together with three flap-like nucleotides, constrains the fluorophore into its active conformation.

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