Outstanding Articles
Structural basis for bacterial lipoprotein relocation by the transporter LolCDE

Lipoproteins in the outer membrane of Gram-negative bacteria are involved in various vital physiological activities, including multidrug resistance. Synthesized in the cytoplasm and matured in the inner membrane, lipoproteins must be transported to the outer membrane through the Lol pathway mediated by the ATP-binding cassette transporter LolCDE in the inner membrane via an unknown mechanism. Here, we report cryo-EM structures of Escherichia coli LolCDE in apo, lipoprotein-bound, LolA-bound, ADP-bound and AMP-PNP-bound states at a resolution of 3.2–3.8 Å, covering the complete lipoprotein transport cycle. Mutagenesis and in vivo viability assays verify features of the structures and reveal functional residues and structural characteristics of LolCDE. The results provide insights into the mechanisms of sorting and transport of outer-membrane lipoproteins and may guide the development of novel therapies against multidrug-resistant Gram-negative bacteria.

2021-03-29

Nat Struct Mol Biol

West China Hospital, SCU

Asymmetric organocatalysis: an enabling technology for medicinal chemistry

The efficacy and synthetic versatility of asymmetric organocatalysis have contributed enormously to the field of organic synthesis since the early 2000s. As asymmetric organocatalytic methods mature, they have extended beyond the academia and undergone scale-up for the production of chiral drugs, natural products, and enantiomerically enriched bioactive molecules. This review provides a comprehensive overview of the applications of asymmetric organocatalysis in medicinal chemistry. A general picture of asymmetric organocatalytic strategies in medicinal chemistry is firstly presented, and the specific applications of these strategies in pharmaceutical synthesis are systematically described, with a focus on the preparation of antiviral, anticancer, neuroprotective, cardiovascular, antibacterial, and antiparasitic agents, as well as several miscellaneous bioactive agents. The review concludes with a discussion of the challenges, limitations and future prospects for organocatalytic asymmetric synthesis of medicinally valuable compounds.

2021-01-26

Chemical Society Reviews

Chengdu University of Traditional Chinese Medicine

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