Abstract：
:Siderophores are iron-chelating molecules produced by microorganisms and plants to acquire exogenous iron. Siderophore biosynthetic enzymology often produces elaborate and unique molecules through unusual reactions to enable specific recognition by the producing organisms. Herein, we report the structure of two siderophore analogs from Agrobacterium fabrum strain C58, which we named fabrubactin (FBN) A and FBN B. Additionally, we characterized the substrate specificities of the NRPS and PKS components. The structures suggest unique Favorskii-like rearrangements of the molecular backbone that we propose are catalyzed by the flavin-dependent monooxygenase, FbnE. FBN A and B contain a 1,1-dimethyl-3-amino-1,2,3,4-tetrahydro-7,8-dihydroxy-quinolin (Dmaq) moiety previously seen only in the anachelin cyanobacterial siderophores. We provide evidence that Dmaq is derived from l-DOPA and propose a mechanism for the formation of the mature Dmaq moiety. Our bioinformatic analyses suggest that FBN A and B and the anachelins belong to a large and diverse siderophore family widespread throughout the Rhizobium/Agrobacterium group, α-proteobacteria, and cyanobacteria.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Vinnik V,Zhang F,Park H,Cook TB,Throckmorton K,Pfleger BF,Bugni TS,Thomas MGdoi
10.1021/acschembio.0c00809subject
Has Abstractpub_date
2021-01-15 00:00:00pages
125-135issue
1eissn
1554-8929issn
1554-8937journal_volume
16pub_type
杂志文章abstract：:Allosteric inhibitors can be more difficult to optimize without an understanding of how their binding influences the conformational motions of the target. Here, we used an integrated computational and experimental approach to probe the molecular mechanism of an allosteric inhibitor of heat shock protein 70 (Hsp70). Th...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.8b00712
更新日期：2018-11-16 00:00:00
abstract：:Synthetic compounds for controlling or creating human immunity have the potential to revolutionize disease treatment. Motivated by challenges in this arena, we report herein a strategy to target metastatic cancer cells for immune-mediated destruction by targeting the urokinase-type plasminogen activator receptor (uPAR...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb200374e
更新日期：2012-02-17 00:00:00
abstract：:Proteotoxicity has long been considered a key factor in mitochondrial dysfunction and human disease. The origin of the endogenous offending toxic substrates and the regulatory pathways to deal with these insults, however, have remained unclear. Mitochondria maintain a compartmentalized gene expression system that in a...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.9b00518
更新日期：2019-11-15 00:00:00
abstract：:Many cellular processes are regulated by posttranslational modifications that are recognized by specific domains in protein binding partners. These interactions are often weak, thus allowing a highly dynamic and combinatorial regulatory network of protein-protein interactions. We report an efficient strategy that over...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb400723j
更新日期：2014-02-21 00:00:00
abstract：:G protein-coupled receptors (GPCRs) are an ubiquitously expressed class of transmembrane proteins involved in the signal transduction of neurotransmitters, hormones and various other ligands. Their signaling output is desensitized by mechanisms involving phosphorylation, internalization, and dissociation from G protei...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb3004513
更新日期：2013-03-15 00:00:00
abstract：:New methodologies for site-specifically radiolabeling proteins with (18)F are required to generate high quality radiotracers for preclinical and clinical applications with positron emission tomography. Herein, we report an approach by which we use lipoic acid ligase (LplA) to conjugate [(18)F]-fluorooctanoic acid to a...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.6b00172
更新日期：2016-06-17 00:00:00
abstract：:The oxidative addition of nitric oxide (NO) to a thiol, S-nitrosation, is a focus of studies on cyclic guanosine monophosphate (cGMP)-independent NO signaling. S-Nitrosation of the catalytic cysteine of the caspase proteases has important effects on apoptosis and consequently has received attention. Here we report on ...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb600393x
更新日期：2006-11-21 00:00:00
abstract：:The remodeling of active sites to generate novel biocatalysts is an attractive and challenging task. We developed a stepwise loop insertion strategy (StLois), in which randomized residue pairs are inserted into active site loops. The phosphotriesterase-like lactonase from Geobacillus kaustophilus (GkaP-PLL) was used t...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.7b00018
更新日期：2017-05-19 00:00:00
abstract：:Chromophore-assisted light inactivation (CALI) is a potentially powerful tool for the acute disruption of a target protein inside living cells with high spatiotemporal resolution. This technology, however, has not been widely utilized, mainly because of the lack of an efficient chromophore as the photosensitizing agen...
journal_title：ACS chemical biology
pub_type： 信件
doi：10.1021/cb100431e
更新日期：2011-05-20 00:00:00
abstract：:Transpeptidases, members of the penicillin-binding protein (PBP) families, catalyze cross-linking of the bacterial cell wall. This transformation is critical for the survival of bacteria, and it is the target of inhibition by β-lactam antibiotics. We report herein our structural insights into catalysis by the essentia...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.7b00817
更新日期：2018-03-16 00:00:00
abstract：:Peptide-recognizing G protein-coupled receptors (GPCRs) are promising therapeutic targets but often resist drug discovery efforts. Determination of crystal structures for peptide-binding GPCRs has provided opportunities to explore structure-based methods in lead development. Molecular docking screens of two chemical l...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.6b00646
更新日期：2017-03-17 00:00:00
abstract：:The LpxC enzyme in the lipid A biosynthetic pathway is one of the most promising and clinically unexploited antibiotic targets for treatment of multidrug-resistant Gram-negative infections. Progress in medicinal chemistry has led to the discovery of potent LpxC inhibitors with a variety of chemical scaffolds and disti...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb400067g
更新日期：2014-01-17 00:00:00
abstract：:Enzymatic transfer of the AMP portion of ATP to substrate proteins has recently been described as an essential mechanism of bacterial infection for several pathogens. The first AMPylator to be discovered, VopS from Vibrio parahemolyticus, catalyzes the transfer of AMP onto the host GTPases Cdc42 and Rac1. Modification...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb4006886
更新日期：2014-02-21 00:00:00
abstract：:We report progress toward a general strategy for mimicking the recognition properties of specific α-helices within natural proteins through the use of oligomers that are less susceptible than conventional peptides to proteolysis. The oligomers contain both α- and β-amino acid residues, with the density of the β subuni...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.5b00109
更新日期：2015-07-17 00:00:00
abstract：:Pentamycin is a polyene antibiotic, registered in Switzerland for the treatment of vaginal candidiasis, trichomoniasis, and mixed infections. Chemical instability has hindered its widespread application and development as a drug. Here, we report the identification of Streptomyces sp. S816, isolated from Philippine man...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.9b00270
更新日期：2019-06-21 00:00:00
abstract：:Sublancin 168 is a member of a small group of glycosylated antimicrobial peptides known as glycocins. The solution structure of sublancin 168, a 37-amino-acid peptide produced by Bacillus subtilis 168, has been solved by nuclear magnetic resonance (NMR) spectroscopy. Sublancin comprises two α-helices and a well-define...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb4008106
更新日期：2014-03-21 00:00:00
abstract：:Mutations in the NPHP1 gene, coding for human nephrocystin-1 (NPHP1), cause the autosomal recessive disease nephronophthisis, the most common cause of end-stage renal disease in children and adolescents. The function and structure of NPHP1 are still poorly characterized. NPHP1 presents a modular structure well in keep...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.9b00582
更新日期：2019-08-16 00:00:00
abstract：:Miniproteins have a size between that of larger biologics and small molecules and presumably possess the advantages of both; they represent an expanding class of promising scaffolds for the design of affinity reagents, enzymes, and therapeutics. Conventional strategies to promote cellular uptake of miniproteins rely o...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.8b00564
更新日期：2018-11-16 00:00:00
abstract：:Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyt...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb700159m
更新日期：2007-11-20 00:00:00
abstract：:Regorafenib (Stivarga) is an oral small molecule kinase inhibitor used to treat metastatic colorectal cancer, hepatocellular carcinomas, and gastrointestinal stromal tumors. Diarrhea is one of the most frequently observed adverse reactions associated with regorafenib. This toxicity may arise from the reactivation of t...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.9b00663
更新日期：2019-12-20 00:00:00
abstract：:Drug resistance continues to be a growing global problem. The efficacy of small molecule inhibitors is threatened by pools of genetic diversity in all systems, including antibacterials, antifungals, cancer therapeutics, and antivirals. Resistant variants often include combinations of active site mutations and distal "...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.9b00370
更新日期：2019-11-15 00:00:00
abstract：:A new chemical method for the traceless labeling of glycoproteins with synthetic boronic acid (BA)-tosyl probes was successfully developed. The BA moiety acts as an affinity head to direct the formation of a cyclic boronate diester with the diol groups of glycans. Following this step, the electrophilic tosyl group is ...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb400631w
更新日期：2014-02-21 00:00:00
abstract：:WS9326A and annimycin are produced by Streptomyces asterosporus DSM 41452. WS9326A is a nonribosomal peptide synthetase-(NRPS-) derived depsipeptide containing a cinnamoyl moiety, while annimycin is a linear polyketide bearing a 2-amino-3-hydroxycyclopent-2-enone (C5N) group. Both gene clusters have been sequenced and...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.9b00351
更新日期：2019-08-16 00:00:00
abstract：:Our immune system constantly samples peptides found inside the body as a means to detect foreign pathogens, infected cells, and tumorous cells. T cells, which carry out the critical task of distinguishing self from nonself peptides, can only survey peptides that are presented by the major histocompatibility complex pr...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb400594q
更新日期：2013-11-15 00:00:00
abstract：:Generating highly selective probes to interrogate protein kinase function in biological studies remains a challenge, and new strategies are required. Herein, we describe the development of the first highly selective and cell-permeable inhibitor of c-Src, a key signaling kinase in cancer. Our strategy involves extensio...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb300172e
更新日期：2012-08-17 00:00:00
abstract：:Terpenes are ubiquitous natural chemicals with diverse biological functions spanning all three domains of life. In specialized metabolism, the active sites of terpene synthases (TPSs) evolve in shape and reactivity to direct the biosynthesis of a myriad of chemotypes for organismal fitness. As most terpene biosynthesi...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.5b00539
更新日期：2015-11-20 00:00:00
abstract：:Caenorhabditis elegans lives in compost and decaying fruit, eats bacteria and is exposed to pathogenic microbes. We show that C. elegans is able to modify diverse microbial small-molecule toxins via both O- and N-glucosylation as well as unusual 3'-O-phosphorylation of the resulting glucosides. The resulting glucosyla...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb300520u
更新日期：2013-02-15 00:00:00
abstract：:Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology. Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conj...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.8b00414
更新日期：2018-08-17 00:00:00
abstract：:Creation of an artificial oscillating gene expression system is one of the most challenging issues in synthetic biology. Here, we constructed a simple system to manipulate gene expression patterns to be circadian, reflecting the intrinsic cellular clock, by fusing a core clock protein, BMAL1 or CLOCK, with a zinc fing...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/cb300432s
更新日期：2012-11-16 00:00:00
abstract：:Several C-β-d-glucopyranosyl azoles have recently been uncovered as among the most potent glycogen phosphorylase (GP) catalytic site inhibitors discovered to date. Toward further exploring their translational potential, ex vivo experiments have been performed for their effectiveness in reduction of glycogenolysis in h...
journal_title：ACS chemical biology
pub_type： 杂志文章
doi：10.1021/acschembio.9b00172
更新日期：2019-07-19 00:00:00
