Structural insights of poly(butylene adipate-co-terephthalate)depolymerases

Poly(butylene adipate-co-terephthalate),PBAT,is one of the most popular plastics nowadays and is becoming a large burden to the environment when PBAT waste is accumulated.Biodegradation of PBAT is an environmentally friendly method to treat PBAT waste.In the past two decades,a couple of microbial strains or mixed strains have been chemically characterized.From this,many PBAT depolymerases have been isolated and further structurally determined.The review we focused on the PBAT depolymerases that have been structurally characterized,including lipases,esterases,and cutinases.We also discussed which shape of the substrate-binding tunnels is beneficial for recognizing and decomposing polymer chains of PBAT,which would be important guidance in directing the designation of PBAT depolymerases.

Application of rotational atherectomy in the drug-eluting stent era

Rotational atherectomy (RA) was introduced in the interventional arena in 1988 as a dedicated device for calcified lesions. Due to the complexity of the technique, the development of alternative methods such as the cutting balloon procedure, and the high restenosis rate of subsequent bare metal stenting in long lesions, its use had later declined. However, with the increasing use of drug-eluting stents (DES) and the aggressive treatment of longer lesions, the number of procedure performed with RA has increased significantly again in recent years. In this article, we reviewed the application of RA in DES era.

Crystal structures of D-psicose 3-epimerase from Clostridium cellulolyticum H10 and its complex with ketohexose sugars

D-Psicose 3-epimerase(DPEase)is demonstrated to be useful in the bioproduction of D-psicose,a rare hexose sugar,from D-fructose,found plenty in nature.Clostridium cellulolyticum H10 has recently been identified as a DPEase that can epimerize D-fructose to yield D-psicose with a much higher conversion rate when compared with the conventionally used DTEase.In this study,the crystal structure of the C.cellulolyticum DPEase was determined.The enzyme assembles into a tetramer and each subunit shows a(β/α)8 TIM barrel fold with a Mn2+metal ion in the active site.Additional crystal structures of the enzyme in complex with substrates/products(D-psicose,D-fructose,D-tagatose and D-sorbose)were also determined.From the complex structures of C.cellulolyticum DPEase with D-psicose and D-fructose,the enzyme has much more interactions with D-psicose than D-fructose by forming more hydrogen bonds between the substrate and the active site residues.Accordingly,based on these ketohexosebound complex structures,a C3-O3 proton-exchange mechanism for the conversion between D-psicose and D-fructose is proposed here.These results provide a clear idea for the deprotonation/protonation roles of E150 and E244 in catalysis.

Discovery of novel covalent selective estrogen receptor degraders against endocrine-resistant breast cancer

Endocrine-resistance remains a major challenge in estrogen receptorαpositive(ERα^(+))breast cancer(BC)treatment and constitutively active somatic mutations in ERαare a common mechanism.There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrineresistance.Given aberrant ERαactivity,we herein report the identification of novel covalent selective estrogen receptor degraders(cSERDs)possessing the advantages of both covalent and degradation strategies.A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERa+breast cancer cell lines including mutant ERα.Crystal structure of ERα-29c complex alongside intact mass spectrometry revealed that 29c disrupted ERa protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11,thus enforcing a unique antagonist conformation and driving the ERαdegradation.These significant effects of the cSERD on ERαhomeostasis,unlike typical ERαdegraders that occur directly via long side chains perturbing the morphology of H12,demonstrating a distinct mechanism of action(MoA).In vivo,29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity.This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.