解剖学和形态学
麻醉学
听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
免疫学
传染病
综合和补充性医学
医学伦理学
医学信息学
医学实验室技术
医学,全科和内科
医学,法律
医学,研究和试验
神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
肿瘤学
眼科学
整形外科学
耳鼻喉科学
病理学
儿科学
周围血管疾病
药理学和药剂学
生理学
基本医疗保健
精神病学
公共、环境和职业卫生
放射学,核医学和医学成像
康复学
生殖生物学
呼吸系统
风湿病学
运动科学
外科学
毒理学
热带医学
泌尿学和肾脏学
病毒学
老年医学
健康政策和服务
心理学,临床
abstract::Proteome integrity depends on the ubiquitin-proteasome system to degrade unwanted or abnormal proteins. In addition to the N-degrons, C-terminal residues of proteins can also serve as degradation signals (C-degrons) that are recognized by specific cullin-RING ubiquitin ligases (CRLs) for proteasomal degradation. FEM1C...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-00703-4
更新日期:2021-01-04 00:00:00
abstract::The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein-protein interactions, MerR TFs are capable of reshapi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-00653-x
更新日期:2021-01-01 00:00:00
abstract::MicroRNAs are evolutionarily conserved small, noncoding RNAs that regulate diverse biological processes. Due to their essential regulatory roles, microRNA biogenesis is tightly regulated, where protein factors are often found to interact with specific primary and precursor microRNAs for regulation. Here, using NMR rel...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-00667-5
更新日期:2021-01-01 00:00:00
abstract::Tyrian purple, mainly composed of 6,6'-dibromoindigo (6BrIG), is an ancient dye extracted from sea snails and was recently demonstrated as a biocompatible semiconductor material. However, its synthesis remains limited due to uncharacterized biosynthetic pathways and the difficulty of regiospecific bromination. Here, w...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-00684-4
更新日期:2021-01-01 00:00:00
abstract::Bifunctional Rel stringent factors, the most abundant class of RelA/SpoT homologs, are ribosome-associated enzymes that transfer a pyrophosphate from ATP onto the 3' of guanosine tri-/diphosphate (GTP/GDP) to synthesize the bacterial alarmone (p)ppGpp, and also catalyze the 3' pyrophosphate hydrolysis to degrade it. T...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-0520-2
更新日期:2020-08-01 00:00:00
abstract::Changes in the cellular environment modulate protein energy landscapes to drive important biology, with consequences for signaling, allostery and other vital processes. The effects of ubiquitination are particularly important because of their potential influence on degradation by the 26S proteasome. Moreover, proteaso...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-0556-3
更新日期:2020-08-01 00:00:00
abstract::Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-0506-0
更新日期:2020-06-01 00:00:00
abstract::Combination antiretroviral therapy has transformed HIV-1 infection, once a fatal illness, into a manageable chronic condition. Drug resistance, severe side effects and treatment noncompliance bring challenges to combination antiretroviral therapy implementation in clinical settings and indicate the need for additional...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-0496-y
更新日期:2020-05-01 00:00:00
abstract::Nature uses a variety of tools to mediate the flow of information in cells, many of which control distances between key biomacromolecules. Researchers have thus generated compounds whose activities stem from interactions with two (or more) proteins simultaneously. In this Perspective, we describe how these 'bifunction...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/s41589-020-0469-1
更新日期:2020-04-01 00:00:00
abstract::Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-0467-3
更新日期:2020-03-01 00:00:00
abstract::Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer's disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternate therapeutic target; however, drug discovery programs focused on this G protein-cou...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0453-9
更新日期:2020-03-01 00:00:00
abstract::Genetic screens in cultured human cells represent a powerful unbiased strategy to identify cellular pathways that determine drug efficacy, providing critical information for clinical development. We used insertional mutagenesis-based screens in haploid cells to identify genes required for the sensitivity to lasonolide...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0447-7
更新日期:2020-02-01 00:00:00
abstract::Pseudouridine synthases (PUSs) are responsible for installation of pseudouridine (Ψ) modification in RNA. However, the activity and function of the PUS enzymes remain largely unexplored. Here we focus on human PUS10 and find that it co-expresses with the microprocessor (DROSHA-DGCR8 complex). Depletion of PUS10 result...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0420-5
更新日期:2020-02-01 00:00:00
abstract::Lysostaphin is a bacteriolytic enzyme targeting peptidoglycan, the essential component of the bacterial cell envelope. It displays a very potent and specific activity toward staphylococci, including methicillin-resistant Staphylococcus aureus. Lysostaphin causes rapid cell lysis and disrupts biofilms, and is therefore...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0393-4
更新日期:2020-01-01 00:00:00
abstract::The catalytic versatility of cytochrome P450 monooxygenases is remarkable. Here, we present mechanistic and structural characterizations of TleB from Streptomyces blastmyceticus and its homolog HinD from Streptoalloteichus hindustanus, which catalyze unusual intramolecular C-N bond formation to generate indolactam V f...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0380-9
更新日期:2019-12-01 00:00:00
abstract::Antibody-drug conjugates (ADCs) selectively deliver chemotherapeutic agents to target cells and are important cancer therapeutics. However, the mechanisms by which ADCs are internalized and activated remain unclear. Using CRISPR-Cas9 screens, we uncover many known and novel endolysosomal regulators as modulators of AD...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0342-2
更新日期:2019-10-01 00:00:00
abstract::Helical membrane proteins are typically assumed to attain stable transmembrane topologies immediately upon co-translational membrane insertion. Here we show that unassembled monomers of the small multidrug resistance (SMR) family exist in a dynamic equilibrium where the N-terminal transmembrane helix flips in and out ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0356-9
更新日期:2019-10-01 00:00:00
abstract::Hundreds of cellular proteins require iron cofactors for activity, and cells express systems for their assembly and distribution. Molecular details of the cytosolic iron pool used for iron cofactors are lacking, but iron chaperones of the poly(rC)-binding protein (PCBP) family play a key role in ferrous ion distributi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0330-6
更新日期:2019-09-01 00:00:00
abstract::BCL-2 family protein interactions regulate apoptosis, a critical process that maintains tissue homeostasis but can cause a host of human diseases when deregulated. Venetoclax is the first FDA-approved drug to reactivate apoptosis in cancer by selectively targeting an anti-apoptotic BCL-2 family member. The drug's acti...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/s41589-019-0306-6
更新日期:2019-07-01 00:00:00
abstract::To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems comp...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0284-8
更新日期:2019-06-01 00:00:00
abstract::The rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0250-5
更新日期:2019-05-01 00:00:00
abstract::Gentamicin B (GB), a valuable starting material for the preparation of the semisynthetic aminoglycoside antibiotic isepamicin, is produced in trace amounts by the wild-type Micromonospora echinospora. Though the biosynthetic pathway to GB has remained obscure for decades, we have now identified three hidden pathways t...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0203-4
更新日期:2019-03-01 00:00:00
abstract:: ...
journal_title:Nature chemical biology
pub_type: 评论,杂志文章
doi:10.1038/s41589-019-0230-9
更新日期:2019-03-01 00:00:00
abstract::Bacterial biofilms can be programmed to produce living materials with self-healing and evolvable functionalities. However, the wider use of artificial biofilms has been hindered by limitations on processability and functional protein secretion capacity. We describe a highly flexible and tunable living functional mater...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0169-2
更新日期:2019-01-01 00:00:00
abstract:: ...
journal_title:Nature chemical biology
pub_type: 评论,杂志文章
doi:10.1038/s41589-018-0199-9
更新日期:2019-01-01 00:00:00
abstract::N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0184-3
更新日期:2019-01-01 00:00:00
abstract:: ...
journal_title:Nature chemical biology
pub_type: 评论,杂志文章
doi:10.1038/s41589-018-0174-5
更新日期:2018-12-01 00:00:00
abstract::Synthetic mRNA is an attractive vehicle for gene therapies because of its transient nature and improved safety profile over DNA. However, unlike DNA, broadly applicable methods to control expression from mRNA are lacking. Here we describe a platform for small-molecule-based regulation of expression from modified RNA (...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0146-9
更新日期:2018-11-01 00:00:00
abstract::Targeted protein degradation via small-molecule modulation of cereblon offers vast potential for the development of new therapeutics. Cereblon-binding therapeutics carry the safety risks of thalidomide, which caused an epidemic of severe birth defects characterized by forelimb shortening or phocomelia. Here we show th...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0129-x
更新日期:2018-10-01 00:00:00
abstract::Cell polarity is the asymmetric compartmentalization of cellular components. An opposing gradient of partitioning-defective protein kinases, atypical protein kinase C (aPKC) and PAR-1, at the cell cortex guides diverse asymmetries in the structure of metazoan cells, but the mechanism underlying their spatial patternin...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0117-1
更新日期:2018-10-01 00:00:00
abstract::The ykkC family of bacterial riboswitches combines several widespread classes that have similar secondary structures and consensus motifs but control different genes in response to different cellular metabolites. Here we report the crystal structures of two distinct ykkC riboswitches specifically bound to their cognat...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0114-4
更新日期:2018-09-01 00:00:00
abstract::Cysteine dioxygenase (CDO) plays an essential role in sulfur metabolism by regulating homeostatic levels of cysteine. Human CDO contains a post-translationally generated Cys93-Tyr157 cross-linked cofactor. Here, we investigated this Cys-Tyr cross-linking by incorporating unnatural tyrosines in place of Tyr157 via a ge...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0085-5
更新日期:2018-09-01 00:00:00
abstract::Nature is a diverse and rich source of bioactive pathways or novel building blocks for synthetic biology. In this Perspective, we describe the emerging research field in which metagenomes are functionally interrogated using synthetic biology. This approach substantially expands the set of identified biological activit...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/s41589-018-0100-x
更新日期:2018-08-01 00:00:00
abstract::Identifying targets of antibacterial compounds remains a challenging step in the development of antibiotics. We have developed a two-pronged functional genomics approach to predict mechanism of action that uses mutant fitness data from antibiotic-treated transposon libraries containing both upregulation and inactivati...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0041-4
更新日期:2018-06-01 00:00:00
abstract:: ...
journal_title:Nature chemical biology
pub_type: 评论,杂志文章
doi:10.1038/s41589-018-0073-9
更新日期:2018-06-01 00:00:00
abstract::Serine hydrolases play diverse roles in regulating host-pathogen interactions in a number of organisms, yet few have been characterized in the human pathogen Staphylococcus aureus. Here we describe a chemical proteomic screen that identified ten previously uncharacterized S. aureus serine hydrolases that mostly lack h...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0060-1
更新日期:2018-06-01 00:00:00
abstract::Intrinsically disordered regions (IDRs) of proteins often regulate function upon post-translational modification (PTM) through interactions with folded domains. An IDR linking two α-helices (α1-α2) of the antiapoptotic protein Bcl-xL experiences several PTMs that reduce antiapoptotic activity. Here, we report that PTM...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0011-x
更新日期:2018-05-01 00:00:00
abstract::The N-end rule pathway senses the N-terminal destabilizing residues of degradation substrates for the ubiquitin-proteasome system, whose integrity shields against various human syndromes including cancer and cardiovascular diseases. GID4, a subunit of the ubiquitin ligase GID complex, has been recently identified as t...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0036-1
更新日期:2018-05-01 00:00:00
abstract::Nonribosomal peptide antibiotics, including polymyxin, vancomycin, and teixobactin, most of which contain D-amino acids, are highly effective against multidrug-resistant bacteria. However, overusing antibiotics while ignoring the risk of resistance arising has inexorably led to widespread emergence of resistant bacter...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0009-4
更新日期:2018-04-01 00:00:00
abstract::Hapalindole alkaloids are a structurally diverse class of cyanobacterial natural products defined by their varied polycyclic ring systems and diverse biological activities. These complex metabolites are generated from a common biosynthetic intermediate by the Stig cyclases in three mechanistic steps: a rare Cope rearr...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0003-x
更新日期:2018-04-01 00:00:00