ACS Chemical Biology最新文献

TRIM21-NUP98 Interface Accommodates Structurally Diverse Molecular Glue Degraders

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-04-09 DOI: 10.1021/acschembio.5c0003610.1021/acschembio.5c00036

Yalong Cheng, Longzhi Cao, Panrui Lu, Lei Xue, Xiaomei Li, Qingyang Wang, Dengfeng Dou, Jin Li and Ting Han*,

{"title":"TRIM21-NUP98 Interface Accommodates Structurally Diverse Molecular Glue Degraders","authors":"Yalong Cheng, Longzhi Cao, Panrui Lu, Lei Xue, Xiaomei Li, Qingyang Wang, Dengfeng Dou, Jin Li and Ting Han*, ","doi":"10.1021/acschembio.5c0003610.1021/acschembio.5c00036","DOIUrl":"https://doi.org/10.1021/acschembio.5c00036https://doi.org/10.1021/acschembio.5c00036","url":null,"abstract":"Molecular glue degraders enable targeted protein degradation by bridging interactions between target proteins and E3 ubiquitin ligases. Whereas some target-E3 interfaces exhibit the capacity to accommodate structurally diverse degraders, the extent of this adaptability across molecular glue targets remains unclear. We recently identified (S)-ACE-OH as a molecular glue degrader that recruits the E3 ubiquitin ligase TRIM21 to the nuclear pore complex by recognizing NUP98, thereby inducing the degradation of nuclear pore proteins. Here, we analyzed public compound toxicity data across a large collection of cell lines and identified two additional molecular glue degraders, PRLX 93936 and BMS-214662, which engage the TRIM21-NUP98 interface to induce selective degradation of nuclear pore proteins. Additionally, we confirmed that HGC652, another TRIM21-dependent molecular glue degrader, also binds at this interface. Together with our previously characterized degrader (S)-ACE-OH, these findings demonstrate that the TRIM21-NUP98 interface can accommodate structurally diverse molecular glue degraders.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 4","pages":"953–959 953–959"},"PeriodicalIF":3.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bringing Histidine Phosphorylation into Light: Role of Chemical Tools.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-04-04 DOI: 10.1021/acschembio.5c00103

Solbee Choi, Shin Hyeon Lee, Jung-Min Kee

引用次数: 0

Bringing Histidine Phosphorylation into Light: Role of Chemical Tools

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-04-04 DOI: 10.1021/acschembio.5c0010310.1021/acschembio.5c00103

Solbee Choi, Shin Hyeon Lee and Jung-Min Kee*,

引用次数: 0

Augmented Acyl-CoA Biosynthesis Promotes Resistance to TEAD Palmitoylation Site Inhibition

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-04-03 DOI: 10.1021/acschembio.5c0016210.1021/acschembio.5c00162

Kayla Nutsch, Marissa N. Trujillo, Lirui Song, Michael A. Erb, Jian Jeffery Chen, James J. Galligan* and Michael J. Bollong*,

引用次数: 0

Augmented Acyl-CoA Biosynthesis Promotes Resistance to TEAD Palmitoylation Site Inhibition.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-04-03 DOI: 10.1021/acschembio.5c00162

Kayla Nutsch, Marissa N Trujillo, Lirui Song, Michael A Erb, Jian Jeffery Chen, James J Galligan, Michael J Bollong

引用次数: 0

Reconstitution and Characterization of Biosynthetic Machinery for Parageocin I, a Novel Thiazole-Rich Peptide from the Thermophilic Bacterium Parageobacillus caldoxylosilyticus.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-04-02 DOI: 10.1021/acschembio.4c00758

Ayane Yano, Hiroya Tomita, Kentaro Miyazaki, Kohsuke Honda

{"title":"Reconstitution and Characterization of Biosynthetic Machinery for Parageocin I, a Novel Thiazole-Rich Peptide from the Thermophilic Bacterium Parageobacillus caldoxylosilyticus.","authors":"Ayane Yano, Hiroya Tomita, Kentaro Miyazaki, Kohsuke Honda","doi":"10.1021/acschembio.4c00758","DOIUrl":"https://doi.org/10.1021/acschembio.4c00758","url":null,"abstract":"Ribosomally synthesized and post-translationally modified peptides (RiPPs) are the representative microbial peptidyl secondary metabolites including the class of linear azol(in)e-containing peptides (LAPs). A substantial proportion of LAPs have been identified in mesophilic microorganisms, including actinomycetes. In this study, we report the biosynthetic reconstitution and characterization of parageocin I, a novel thiazole-rich LAP derived from the thermophilic bacterium Parageobacillus caldoxylosilyticus KH1-5 which exhibits optimal growth around 60 °C. The biosynthetic gene cluster (pgc) consists of four genes: pgcA, pgcB, pgcC, and pgcD, encoding the precursor peptide, dehydrogenase, YcaO family cyclodehydratase, and biosynthetic scaffold protein, respectively. The precursor peptide PgcA possesses 13 Cys and 2 Ser residues, with regularly repeated sequences interspaced between Cys residues. We first reconstituted the biosynthesis heterologously in Escherichia coli. Mass spectrometry analysis of the synthesized peptide, coupled with mutational analyses of the modified PgcA, revealed that the final product, designated as parageocin I, harbors 13 thiazole rings derived from the cyclization of Cys residues, while Ser residues remain intact. Furthermore, mutational studies of PgcA revealed three key principles governing heterocyclization by PgcC: (i) Cys is acceptable, but Ser and Thr are not; (ii) the presence of an acidic amino acid preceding Cys is not permissible; and (iii) a minimum of two amino acids must separate Cys residues. In addition, we successfully reconstituted the biosynthesis in vitro using the purified recombinant enzymes. This is the first report of LAP biosynthesis in thermophilic Bacillaceae, thereby expanding our understanding of not only LAPs but also secondary metabolism in thermophiles.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Noninvasive Bioluminescence Imaging of Serum Albumins in Living Mice.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-04-02 DOI: 10.1021/acschembio.4c00740

Sung-Bae Kim, Genta Kamiya, Tadaomi Furuta, Nobuo Kitada, Suresh Thangudu, Arutselvan Natarajan, Shojiro A Maki, Ramasamy Paulmurugan

{"title":"Noninvasive Bioluminescence Imaging of Serum Albumins in Living Mice.","authors":"Sung-Bae Kim, Genta Kamiya, Tadaomi Furuta, Nobuo Kitada, Suresh Thangudu, Arutselvan Natarajan, Shojiro A Maki, Ramasamy Paulmurugan","doi":"10.1021/acschembio.4c00740","DOIUrl":"https://doi.org/10.1021/acschembio.4c00740","url":null,"abstract":"Bioluminescence (BL) is an emerging optical readout that has been extensively used in various bioassays and molecular imaging systems. In this study, we present the bioanalytical application of marine luciferins as an excellent optical indicator for noninvasive imaging of serum albumins. We synthesized 30 kinds of regioisomeric coelenterazine (CTZ) analogs and investigated their specificities for major serum proteins from various species. The results found that some of the CTZ analogs exhibited surprisingly specific optical signals upon binding with the serum albumins. These CTZ analogs showed diverse emission spectra ranging from 495 to 558 nm according to the albumin species used acting as pseudoluciferases. The selective albumin indicators, TS1 and TS2, exhibited long and linear dose-response curves and were sensitive enough to determine clinically normal and abnormal (microalbuminuria) ranges of albumins in saliva and urine. The sensitivity of this assay is superior to that of the conventional Bromocresol purple (BCP) method. We further demonstrated the advantages of the albumin indicators through noninvasive imaging of liver-albumin in vivo in living mice. The in vivo and ex vivo imaging results confirmed that the CTZ analog TS2 can sensitively image the liver-albumin in vivo with high signal-to-background ratio. This study paves a new way to make use of CTZ analogs for noninvasive albumin imaging and conceptualizes the pseudoluciferase-based imaging. The distinct in vivo imaging of serum albumins can potentially aid clinicians in providing insight into patients' liver function and other vital factors needed for whole-body homeostasis.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering the Specificity of Acetyl-CoA Synthetase for Diverse Acyl-CoA Thioester Generation

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-04-02 DOI: 10.1021/acschembio.5c0001410.1021/acschembio.5c00014

Jared R. Cossin, Thaddeus Q. Paulsel, Kim Castelli, Breck Wcisel, Alexandra A. Malico and Gavin J. Williams*,

{"title":"Engineering the Specificity of Acetyl-CoA Synthetase for Diverse Acyl-CoA Thioester Generation","authors":"Jared R. Cossin, Thaddeus Q. Paulsel, Kim Castelli, Breck Wcisel, Alexandra A. Malico and Gavin J. Williams*, ","doi":"10.1021/acschembio.5c0001410.1021/acschembio.5c00014","DOIUrl":"https://doi.org/10.1021/acschembio.5c00014https://doi.org/10.1021/acschembio.5c00014","url":null,"abstract":"CoA thioesters are valuable intermediates in numerous biosynthetic routes and metabolic processes. However, diversifying these compounds and their corresponding downstream products hinges on broadening the promiscuity of CoA ligases that produce them or using additional enzymes to functionalize them. Here, the inherent promiscuity of an acyl-CoA ligase from Pseudomonas chlororaphis was probed with carboxylic acids of varying sizes and functionality. The enzyme was engineered to improve its activity with a diverse panel of acyl-CoA thioesters, including halogenated and oxidized acids, that can be used in downstream biosynthetic production strategies. To demonstrate the utility of the engineered enzyme, a subset of the substrates was leveraged for the complete in situ biosynthesis of a small panel of pyrones via a portion of the archetypal polyketide synthase (PKS), 6-deoxyerythronolide B synthase (DEBS). This approach supports probing the promiscuity of polyketide biosynthesis and the diversification of natural product scaffolds.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 4","pages":"930–941 930–941"},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Noninvasive Bioluminescence Imaging of Serum Albumins in Living Mice

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-04-02 DOI: 10.1021/acschembio.4c0074010.1021/acschembio.4c00740

Sung-Bae Kim*, Genta Kamiya, Tadaomi Furuta, Nobuo Kitada, Suresh Thangudu, Arutselvan Natarajan, Shojiro A. Maki and Ramasamy Paulmurugan,

{"title":"Noninvasive Bioluminescence Imaging of Serum Albumins in Living Mice","authors":"Sung-Bae Kim*, Genta Kamiya, Tadaomi Furuta, Nobuo Kitada, Suresh Thangudu, Arutselvan Natarajan, Shojiro A. Maki and Ramasamy Paulmurugan, ","doi":"10.1021/acschembio.4c0074010.1021/acschembio.4c00740","DOIUrl":"https://doi.org/10.1021/acschembio.4c00740https://doi.org/10.1021/acschembio.4c00740","url":null,"abstract":"Bioluminescence (BL) is an emerging optical readout that has been extensively used in various bioassays and molecular imaging systems. In this study, we present the bioanalytical application of marine luciferins as an excellent optical indicator for noninvasive imaging of serum albumins. We synthesized 30 kinds of regioisomeric coelenterazine (CTZ) analogs and investigated their specificities for major serum proteins from various species. The results found that some of the CTZ analogs exhibited surprisingly specific optical signals upon binding with the serum albumins. These CTZ analogs showed diverse emission spectra ranging from 495 to 558 nm according to the albumin species used acting as pseudoluciferases. The selective albumin indicators, TS1 and TS2, exhibited long and linear dose–response curves and were sensitive enough to determine clinically normal and abnormal (microalbuminuria) ranges of albumins in saliva and urine. The sensitivity of this assay is superior to that of the conventional Bromocresol purple (BCP) method. We further demonstrated the advantages of the albumin indicators through noninvasive imaging of liver-albumin in vivo in living mice. The in vivo and ex vivo imaging results confirmed that the CTZ analog TS2 can sensitively image the liver-albumin in vivo with high signal-to-background ratio. This study paves a new way to make use of CTZ analogs for noninvasive albumin imaging and conceptualizes the pseudoluciferase-based imaging. The distinct in vivo imaging of serum albumins can potentially aid clinicians in providing insight into patients’ liver function and other vital factors needed for whole-body homeostasis.","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 4","pages":"802–814 802–814"},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering the Specificity of Acetyl-CoA Synthetase for Diverse Acyl-CoA Thioester Generation.

IF 3.5 2区生物学

ACS Chemical Biology Pub Date : 2025-04-02 DOI: 10.1021/acschembio.5c00014

Jared R Cossin, Thaddeus Q Paulsel, Kim Castelli, Breck Wcisel, Alexandra A Malico, Gavin J Williams

引用次数: 0