Abstract:
:Bioinorganic chemistry remains a vibrant discipline at the interface of chemistry and the biological sciences. Metal ions function in numerous metalloenzymes, are incorporated into pharmaceuticals and imaging agents, and inspire the synthesis of catalysts used to achieve many chemical transformations.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Lippard SJdoi
10.1038/nchembio1006-504subject
Has Abstractpub_date
2006-10-01 00:00:00pages
504-7issue
10eissn
1552-4450issn
1552-4469pii
nchembio1006-504journal_volume
2pub_type
杂志文章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::The inability of cells to properly fold, modify and assemble secretory and transmembrane proteins leads to accumulation of misfolded proteins in the endoplasmic reticulum (ER). Under these conditions of 'ER stress', cell survival depends on homeostatic benefits from an intracellular signaling pathway called the unfold...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.1664
更新日期:2014-11-01 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::Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2538
更新日期:2018-02-01 00:00:00
abstract::The streptothricin (ST) antibiotics, produced by Streptomyces bacteria, contain L-β-lysine ((3S)-3,6-diaminohexanoic acid) oligopeptides as pendant chains. Here we describe three unusual nonribosomal peptide synthetases (NRPSs) involved in ST biosynthesis: ORF 5 (a stand-alone adenylation (A) domain), ORF 18 (containi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1040
更新日期:2012-09-01 00:00:00
abstract::The chemical scaffolds from which screening libraries are built have strong influence on the libraries' utility for screening campaigns. Here we present analysis of the scaffold composition of several types of commercially available screening collections and compare those compositions to those of drugs and drug candid...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio0807-442
更新日期:2007-08-01 00:00:00
abstract::Liver X receptors (Lxrα and Lxrβ) are ligand-dependent nuclear receptors critical for ventral midbrain neurogenesis in vivo. However, no endogenous midbrain Lxr ligand has so far been identified. Here we used LC/MS and functional assays to identify cholic acid as a new Lxr ligand. Moreover, 24(S),25-epoxycholesterol (...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1156
更新日期:2013-02-01 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::Improved methods for studying intracellular reactive Fe(II) are of significant interest for studies of iron metabolism and disease-relevant changes in iron homeostasis. Here we describe a highly selective reactivity-based probe in which a Fenton-type reaction with intracellular labile Fe(II) leads to unmasking of the ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2116
更新日期:2016-09-01 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::Secondary structure refolding is a key event in biology as it modulates the conformation of many proteins in the cell, generating functional or aberrant states. The crystal structures of mannosyltransferase PimA reveal an exceptional flexibility of the protein along the catalytic cycle, including β-strand-to-α-helix a...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1694
更新日期:2015-01-01 00:00:00
abstract::Designing selective inhibitors of proteases has proven problematic, in part because pharmacophores that confer potency exploit the conserved catalytic apparatus. We developed a fundamentally different approach by designing irreversible inhibitors that target noncatalytic cysteines that are structurally unique to a tar...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.492
更新日期:2011-01-01 00:00:00
abstract::Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.673
更新日期:2011-10-09 00:00:00
abstract::Identifying the interaction partners of noncoding RNAs is essential for elucidating their functions. We have developed an approach, termed microRNA crosslinking and immunoprecipitation (miR-CLIP), using pre-miRNAs modified with psoralen and biotin to capture their targets in cells. Photo-crosslinking and Argonaute 2 i...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1713
更新日期:2015-02-01 00:00:00
abstract::The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. Herein, we introduce the first orally bioavailable pan-WNK-kinase inhibitor, WNK463, that exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. I...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2168
更新日期:2016-11-01 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::We report a salvage pathway in Gram-negative bacteria that bypasses de novo biosynthesis of UDP N-acetylmuramic acid (UDP-MurNAc), the first committed peptidoglycan precursor, and thus provides a rationale for intrinsic fosfomycin resistance. The anomeric sugar kinase AmgK and the MurNAc α-1-phosphate uridylyl transfe...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1289
更新日期:2013-08-01 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::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::Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When we applied the approach to nonri...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2207
更新日期:2016-12-01 00:00:00
abstract::Studies of gene function and molecular mechanisms in Plasmodium falciparum are hampered by difficulties in characterizing and measuring phenotypic differences between individual parasites. We screened seven parasite lines for differences in responses to 1,279 bioactive chemicals. Hundreds of compounds were active in i...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.215
更新日期:2009-10-01 00:00:00
abstract::We document a new dimension of surface recognition in which communication is controlled through the collective behavior of lipids. Membrane cholesterol induces a tilt in glycolipid receptor headgroup, resulting in loss of access for ligand binding. This property appears to organize erythrocyte blood group presentation...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.551
更新日期:2011-05-01 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::Learning regulatory networks from genomics data is an important problem with applications spanning all of biology and biomedicine. Functional genomics projects offer a cost-effective means of greatly expanding the completeness of our regulatory models, and for some prokaryotic organisms they offer a means of learning ...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.122
更新日期:2008-11-01 00:00:00
abstract::Specific chemicals can prime the plant immune system for augmented defense. β-aminobutyric acid (BABA) is a priming agent that provides broad-spectrum disease protection. However, BABA also suppresses plant growth when applied in high doses, which has hampered its application as a crop defense activator. Here we descr...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1520
更新日期:2014-06-01 00:00:00
abstract::Mammals that degrade uric acid are not affected by gout or urate kidney stones. It is not fully understood how they convert uric acid into the much more soluble allantoin. Until recently, it had long been thought that urate oxidase was the only enzyme responsible for this conversion. However, detailed studies of the m...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio768
更新日期:2006-03-01 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::Enzyme-catalyzed peptide ligation is a powerful tool for site-specific protein bioconjugation, but stringent enzyme-substrate specificity limits its utility. We developed an approach for comprehensively characterizing peptide ligase specificity for N termini using proteome-derived peptide libraries. We used this strat...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2521
更新日期:2018-01-01 00:00:00
abstract::Concatenation of engineered biocatalysts into multistep pathways markedly increases their utility, but the development of generalizable assembly methods remains a major challenge. Herein we evaluate 'bioretrosynthesis', which is an application of the retrograde evolution hypothesis, for biosynthetic pathway constructi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1494
更新日期:2014-05-01 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