2024
Sacco MD, Hammond LR, Noor RE, Bhattacharya D, McKnight LJ, Madsen JJ, Zhang X, Butler SG, Kemp MT, Jaskolka-Brown AC, Khan SJ, Gelis I, Eswara P, Chen Y. Staphylococcus aureus FtsZ and PBP4 bind to the conformationally dynamic N-terminal domain of GpsB. Elife. 2024. PubMed, PDB 8E2B, 8E2C
Jacobs LMC, Consol P, Chen Y. Drug Discovery in the Field of β-lactams: An Academic Perspective. Antibiotics. 2024. PubMed
2023
Jiang W, Abdulkadir S, Zhao X, Sang P, Tomatsidou A, Zhang X, Chen Y, Calcul L, Sun X, Cheng F, Hu Y, Cai J. Inhibition of Hypoxia-Inducible Transcription Factor (HIF-1α) Signaling with Sulfonyl-γ-AApeptide Helices. J Am Chem Soc. 2023. PubMed
Ou J, Lewandowski EM, Hu Y, Lipinski AA, Aljasser A, Colon-Ascanio M, Morgan RT, Jacobs LMC, Zhang X, Bikowitz MJ, Langlais PR, Tan H, Wang J, Chen Y, Choy JS. A yeast-based system to study SARA-CoV-2 Mpro structure and to identify nirmatrelvir resistant mutations. PLoS Pathog. 2023. PubMed, PDB 8DDI, 8DDM
Hu Y, Lewandowski EM, Tan H, Zhang X, Morgan RT, Zhang X, Jacobs LMC, Butler SG, Gongora MV, Choy J, Deng X, Chen Y, Wang J. Naturally Occurring Mutations of SARS-CoV-2 Main Protease Confer Drug Resistance to Nirmatrelvir. ACS Cent. Sci. 2023. PubMed, PDB 8D4J, 8D4K, 8D4L, 8D4M, 8D4N, 8DCZ, 8DD1, 8DD9, 8DFE, 8DFN, 8DGB
Tan B, Sacco MD, Tan H, Li K, Joyce R, Zhang X, Chen Y, Wang J. Exploring Diverse Reactive Warheads for the Design of SARS-CoV-2 Main Protease Inhibitors. Eur. J. Med. Chem. 2023. PubMed, PDB 8FIV, 8FIW
Wang L, Ma C, Sacco MD, Xue S, Mahmoud M, Calcul L, Chen Y, Wang J, Cai J. Development of the Safe and Broad-Spectrum Aldehyde and Ketoamide Mpro inhibitors Derived from the Constrained α, γ-AA Peptide Scaffold. Chem. Eur. J. 2023. PubMed, PDB 8DZB, 8DZC
2022
Sacco MD, Wang S, Adapa SR, Zhang X, Lewandowski EM, Gongora MV, Keramisanou D, Atlas ZD, Townsend JA, Gatdula JR, Morgan RT, Hammond LR, Marty MT, Wang J, Eswara PJ, Gelis I, Jiang RHY, Sun X, Chen Y. A unique class of Zn2+-binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile. Nat. Commun. 2022. PubMed, PDB 7RCW, 7RCX, 7RCY, 7RCZ, 7RD0
Sacco MD, Defrees K, Zhang X, Lawless W, Nwanochie E, Balsizer A, Darch SE, Renslo AR, Chen Y. Structure-Based Ligand Design Targeting Pseudomonas aeruginosa LpxA in Lipid A Biosynthesis. ACS Infect. Dis. 2022. PubMed, PDB 7T5R, 7T5S, 7T5X, 7T5Z, 7T60, 7T61
Hammond LR, Sacco MD, Khan SJ, Spanoudis C, Hough-Neidig A, Chen Y, Eswara PJ. GpsB Coordinates Cell Division and Cell Surface Decoration by Wall Teichoic Acids in Staphylococcus aureus. Microbiol Spectr. 2022. PubMed
Sacco MD, Hu Y, Gongora MV, Meilleur F, Kemp MT, Zhang X, Wang J, Chen Y. The P132H mutation in the main protease of Omicron SARS-
CoV-2 decreases thermal stability without compromising catalysis or small-molecule drug inhibition. Cell Res. 2022. PubMed, PDB 7TOB
Lewandowski EM, Kroeck KG, Jacobs LMC, Fenske T, Witt RN, Hintz AM, Ramsden ER, Zhang X, Peterson FC, Volkman BF, Veldkamp CT, Chen Y. Structural Insights into Molecular Recognition by Human Chemokine CCL19. Biochemistry. 2022. PubMed, PDB 7STA
2021
Ma C, Xia Z, Sacco MD, Hu Y, Townsend JA, Meng X, Choza J, Tan H, Jang J, Gongora MV, Zhang X, Zhang F, Xiang Y, Marty MT, Chen Y, Wang J. Discovery of Di- and Trihaloacetamides as Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity. J Am Chem Soc. 2021. PubMed, PDB 7RN0, 7RN1
Kemp MT, Nichols DA, Zhang X, Defrees K, Na I, Renslo AR, Chen Y. Mutation of the Conserved Asp-Asp Pair Imparts the Structure, Function, and Inhibition of CTX-M Class A β-lactamase. FEBS Lett. 2021. PubMed, PDB 6D7I, 6D7H, 7S0V
Kuznik NC, Solozobova V, Jung N, Grable S, Lei Q, Lewandowski EM, Munuganti RSN, Zoubeidi A, Chen Y, Brase S, Cato ACB. Development of Benzothiazole Scaffold-Based Androgen Receptor N-Terminal Inhibitor for Treating Androgen-Responsive Prostate Cancer. ACS Chem Biol. 2021. PubMed
Ma C, Sacco MD, Xia Z, Lambrinidis G, Townsend JA, Hu Y, Meng X, Szeto T, Ba M, Zhang X, Gongora M, Zhang F, Marty MT, Xiang Y, Kolocouris A, Chen Y, Wang J. Discovery of SARS-CoV-2 Papain-like Protease Inhibitors through a Combination of High-Throughput Screening and a FlipGFP-Based Reporter Assay. ACS Cent Sci. 2021. PubMed, PDB 7JRN
Expedited Approach toward the Rational Design of Noncovalent SARS-CoV-2 Main Protease Inhibitors. J Med Chem. 2021. PubMed, PDB 7KX5
Low barrier hydrogen bonds in protein structure and function. Biochim Biophys Acta Proteins Proteom. 2021. PubMed
KPC-2 β-lactamase Enables Carbapenem Antibiotic Resistance Through Fast Deacylation of the Covalent Intermediate. J Biol Chem. 2021. PubMed, PDB 6XD5, 6XD7, 6XJ8
2020
N-Hydroxyformamide LpxC inhibitors, their in vivo efficacy in a mouse Escherichia coli infection model, and their safety in a rat hemodynamic assay. Bioorg Med Chem. 2020. PubMed, PDB 7K99
Structure and inhibition of the SARS-CoV-2 main protease reveal strategy for developing dual inhibitors against Mpro and cathepsin L. Sci Adv. 2020. PubMed, PDB 6XA4, 6XFN, 6XBG, 6XBH, 6XBI
Discovery of an Orally Available Diazabicyclooctane Inhibitor (ETX0282) of Class A, C, and D Serine β-Lactamases. J Med Chem. 2020. PubMed, PDB 6VHS
Structural Basis and Binding Kinetics of Vaborbactam in Class A β-Lactamase Inhibition. Antimicrob Agents Chemother. 2020. PubMed, PDB 6V7H, 6V7I
Brzozowski RS, Tomlinson BR, Sacco MD, Chen JJ, Ali AN, Chen Y, Shaw LN, Eswara PJ. Interdependent YpsA- and YfhS-Mediated Cell Division and Cell Size Phenotypes in Bacillus subtilis. mSphere. 2020. PubMed
Hecker SJ, Reddy KR, Lomovskaya O, Griffith DC, Rubio-Aparicio D, Nelson K, Tsivkovski R, Sun D, Sabet M, Tarazi Z, Parkinson J, Totrov M, Boyer SH, Glinka TW, Pemberton OA, Chen Y, Dudley MN. Discovery of Cyclic Boronic Acid QPX7728, an Ultra-broad-spectrum Inhibitor of Serine and Metallo Beta-lactamases. J Med Chem. 2020. PubMed, PDB 6V1J, 6V1M, 6V1O, 6V1P
O’Flynn BG, Lewandowski EM, Prins KC, Suarez G, McCaskey AN, Rios-Guzman NM, Anderson RL, Shepherd BA, Gelis I, Leahy JW, Chen Y, Merkler DJ. Characterization of Arylalkylamine N-Acyltransferase from Tribolium castaneum: An Investigation into a Potential Next-Generation Insecticide Target. ACS Chem Biol. 2020. PubMed, PDB 6V3T
Lewandowski EM, Szczupak Ł, Kowalczyk A, Mendoza G, Arruebo M, Jacobs LMC, Stączek P, Chen Y, Kowalski K. Metallocenyl 7-ACA Conjugates: Antibacterial Activity Studies and Atomic-Resolution X-ray Crystal Structure with CTX-M β-Lactamase. ChemBioChem. 2020. PubMed, PDB 6VNU
Ma C, Sacco MD, Hurst B, Townsend JA, Hu Y, Szeto T, Zhang X, Tarbet B, Marty MT, Chen Y, Wang Y. Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Research. 2020. PubMed, PDB 6WTT
Pemberton OA, Noor RE, Kumar M V V, Sanishvili R, Kemp MT, Kearns FL, Woodcock HL, Gelis I, Chen Y. Mechanism of proton transfer in class A β-lactamase catalysis and inhibition by avibactam. Proc Natl Acad Sci U S A. 2020. PubMed, PDB 6MZ1, 6MZ2
Pennington JM, Kemp M, McGarry L, Chen Y, Stroupe ME. Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site. Nat Commun. 2020. PubMed
Akhtar A, Pemberton OA, Chen Y. Structural basis for substrate specificity and carbapenemase activity of OXA-48 Class D β-lactamase. ACS Infect Dis. 2020. PubMed, PDB 6PQI, 6PT5, 6PSG, 6PT1, 6PTU, 6PK0
2019
Sacco MD, Kroeck KG, Kemp MT, Zhang X, Andrews LD, Chen Y. Influence of the α-Methoxy Group on the Reaction of Temocillin with Pseudomonas aeruginosa PBP3 and CTX-M-14 β-Lactamase. Antimicrob Agents Chemother. 2019. PubMed, PDB 6UN1, 6UN3, 6UNB
Kim MY, Na I, Kim JS, Son SH, Choi S, Lee SE, Kim JH, Jang K, Alterovitz G, Chen Y, van der Vaart A, Won HS, Uversky VN, Kim CG. Rational discovery of antimetastatic agents targeting the intrinsically disordered region of MBD2. Sci Adv. 2019. PubMed
Woo JA, Castaño M, Goss A, Kim D, Lewandowski EM, Chen Y, Liggett SB. Differential long-term regulation of TAS2R14 by structurally distinct agonists. FASEB J. 2019. PubMed
Kroeck KG, Sacco MD, Smith EW, Zhang X, Shoun D, Akhtar A, Darch SE, Cohen F, Andrews LD, Knox JE, Chen Y. Discovery of dual-activity small-molecule ligands of Pseudomonas aeruginosa LpxA and LpxD using SPR and X-ray crystallography. Sci Rep. 2019. PubMed, PDB 6UEC, 6UED, 6UEE, 6UEG
Pemberton OA, Jaishankar P, Akhtar A, Adams JL, Shaw LN, Renslo AR, Chen Y. Heteroaryl Phosphonates as Noncovalent Inhibitors of Both Serine- and Metallocarbapenemases. J Med Chem. 2019. PubMed, PDB 6D15, 6D16, 6D17, 6D18, 6D19, 6D1A, 6D1B, 6D1C, 6D1D, 6D1E, 6D1F, 6D1G, 6D1H, 6D1I, 6D1J, 6D1K, 6DD0, 6DD1, 6O3R, 6NY7, 6O5T
Torelli NJ, Akhtar A, DeFrees K, Jaishankar P, Pemberton OA, Zhang X, Johnson C, Renslo AR, Chen Y. Active-Site Druggability of Carbapenemases and Broad-Spectrum Inhibitor Discovery. ACS Infect Dis. 2019. PubMed, PDB 6M7I, 6MNP, 6MLL, 6MEY, 6MD8, 6MIA, 6MDU, 6EFJ
DeFrees K, Kemp M, ElHilali-Pollard X, Zhang X, Mohamed A, Chen Y, Renslo A. An empirical study of amide–heteroarene π-stacking interactions using reversible inhibitors of a bacterial serine hydrolase. Org. Chem. Front. 2019. PubMed, PDB 6OOE, 6OOF, 6OOH, 6OOJ, 6OOK
2018
Pemberton OA, Zhang X, Nichols DA, DeFrees K, Jaishankar P, Bonnet R, Adams J, Shaw LN, Renslo AR, Chen Y. Antibacterial Spectrum of a Tetrazole-Based Reversible Inhibitor of Serine β-Lactamases. Antimicrob Agents Chemother. 2018. PubMed, PDB 6BT6, 6BU3
Lewandowski EM, Lethbridge KG, Sanishvili R, Skiba J, Kowalski K, Chen Y. Mechanisms of proton relay and product release by Class A β-lactamase at ultrahigh resolution. FEBS J. 2018. PubMed, PDB 5TOP, 5TOY, 5VLE
2017
Dempsey DR, Nichols DA, Battistini MR, Pemberton O, Ospina SR, Zhang X, Carpenter AM, O’Flynn BG, Leahy JW, Kanwar A, Lewandowski EM, Chen Y, Merkler DJ. Structural and Mechanistic Analysis of Drosophila melanogaster Agmatine N-Acetyltransferase, an Enzyme that Catalyzes the Formation of N-Acetylagmatine. Sci Rep. 2017. PubMed, PDB 5K9N
Pemberton OA, Zhang X, Chen Y. Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2). J Med Chem. 2017. PubMed, PDB 5UJ3, 5UJ4, 5UL8
Lewandowski EM, Szczupak Ł, Wong S, Skiba J, Guśpiel A, Solecka J, Vrček V, Kowalski K, Chen Y. Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase. Organometallics. 2017. PubMed, PDB 5UJO
2016
Smith EW, Lewandowski EM, Moussouras NA, Kroeck KG, Volkman BF, Veldkamp CT, Chen Y. Crystallographic structure of truncated CCL21 and putative sulfotyrosine-binding site. Biochemistry. 2016. PubMed, PDB 5EKI
Smith EW, Nevins AM, Qiao Z, Liu Y, Getschman AE, Vankayala SL, Kemp MT, Peterson FC, Li R, Volkman BF, Chen Y. Structure-Based Identification of Novel Ligands Targeting Multiple Sites within a Chemokine-G-Protein-Coupled-Receptor Interface. J Med Chem. 2016. PubMed
2015
Smith, EW, Zhang, X, Behzadi, C, Andrews, L, Cohen, F, Chen, Y. Structures of Pseudomonas aeruginosa LpxA Reveal the Basis for Its Substrate Selectivity. Biochemistry, 2015;54(38):5937-48. PubMed, PDB 5DEM, 5DEP, 5DG3
Nichols DA, Hargis JC, Sanishvili R, Jaishankar P, Defrees K, Smith EW, Wang KK, Prati F, Renslo AR, Woodcock HL, Chen Y. Ligand-Induced Proton Transfer and Low-Barrier Hydrogen Bond Revealed by X-ray Crystallography. J Am Chem Soc. 2015. PubMed, PDB 4UA6, 4UA7, 4UA9, 4UAA
Lewandowski EM, Skiba J, Torelli NJ, Rajnisz A, Solecka J, Kowalski K, Chen Y. Antibacterial properties and atomic resolution X-ray complex crystal structure of a ruthenocene conjugated β-lactam antibiotic. Chem Commun. 2015. PubMed, PDB 4XXR
2014
Smith EW, Liu Y, Getschman AE, Peterson FC, Ziarek JJ, Li R, Volkman BF, Chen Y. Structural Analysis of a Novel Small Molecule Ligand Bound to the CXCL12 Chemokine. J Med Chem. 2014. PubMed, PDB 4UAI
Hargis JC, White JK, Chen Y, Woodcock HL. Can molecular dynamics and QM/MM solve the penicillin binding protein protonation puzzle?. J Chem Inf Model. 2014. PubMed
Nichols DA, Renslo AR, Chen Y. Fragment-based inhibitor discovery against β-lactamase. Future Med Chem. 2014. PubMed
2013
Hung MS, Xu Z, Chen Y, Smith E, Mao JH, Hsieh D, Lin YC, Yang CT, Jablons DM, You L. Hematein, a casein kinase II inhibitor, inhibits lung cancer tumor growth in a murine xenograft model. Int J Oncol. 2013. PubMed
Smith JD, Kumarasiri M, Zhang W, Hesek D, Lee M, Toth M, Vakulenko S, Fisher JF, Mobashery S, Chen Y. Structural analysis of the role of Pseudomonas aeruginosa penicillin-binding protein 5 in β-lactam resistance. Antimicrob Agents Chemother. 2013. PubMed, PDB 4K91
2012
Ziarek JJ, Liu Y, Smith E, Zhang G, Peterson FC, Chen J, Yu Y, Chen Y, Volkman BF, Li R. Fragment-based optimization of small molecule CXCL12 inhibitors for antagonizing the CXCL12/CXCR4 interaction. Curr Top Med Chem. 2012. PubMed
Nichols DA, Jaishankar P, Larson W, Smith E, Liu G, Beyrouthy R, Bonnet R, Renslo AR, Chen Y. Structure-based design of potent and ligand-efficient inhibitors of CTX-M class A β-lactamase. J Med Chem. 2012. PubMed, PDB 4DE3, 4DDY, 4DDS, 4DE2, 4DE0, 4DE1
2011
Tomanicek SJ, Wang KK, Weiss KL, Blakeley MP, Cooper J, Chen Y, Coates L. The active site protonation states of perdeuterated Toho-1 beta-lactamase determined by neutron diffraction support a role for Glu166 as the general base in acylation. FEBS letters. 2011. PubMed
De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL, Suro RM, Garza KM, Lee S, Kim YS, Chen Y, Ning YM, Riggs DL, Fletterick RJ, Guy RK, Trepel JB, Neckers LM, Cox MB. Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells. Proceedings of the National Academy of Sciences. 2011. PubMed
2010
Tomanicek SJ, Blakeley MP, Cooper J, Chen Y, Afonine PV, Coates L. Neutron diffraction studies of a class A beta-lactamase Toho-1 E166A/R274N/R276N triple mutant. J Mol Biol. 2010. PubMed
Veldkamp CT, Ziarek JJ, Peterson FC, Chen Y, Volkman BF. Targeting SDF-1/CXCL12 with a ligand that prevents activation of CXCR4 through structure-based drug design. J Am Chem Soc. 2010. PubMed
Chen,Y, Pohlhaus, DT. In silico docking and scoring of fragments Drug Discovery Today: Technologies. 2010. PubMed
2009
Chen Y, Mcreynolds A, Shoichet BK. Re-examining the role of Lys67 in class C beta-lactamase catalysis. Protein Sci. 2009. PubMed, PDB 3FKV, 3FKW
Chen Y, Zhang W, Shi Q, Hesek D, Lee M, Mobashery S, Shoichet BK. Crystal structures of penicillin-binding protein 6 from Escherichia coli. J Am Chem Soc. 2009. PubMed, PDB 3IT9, 3ITA, 3ITB
Chen Y, Shoichet BK. Molecular docking and ligand specificity in fragment-based inhibitor discovery. Nat Chem Biol. 2009. PubMed
2008
Delmas J, Chen Y, Prati F, Robin F, Shoichet BK, Bonnet R. Structure and dynamics of CTX-M enzymes reveal insights into substrate accommodation by extended-spectrum beta-lactamases. J Mol Biol. 2008. PubMed
2007
Chen Y, Bonnet R, Shoichet BK. The acylation mechanism of CTX-M beta-lactamase at 0.88 a resolution. J Am Chem Soc. 2007. PubMed, PDB 2P74
Whiteson KL, Chen Y, Chopra N, Raymond AC, Rice PA. Identification of a potential general acid/base in the reversible phosphoryl transfer reactions catalyzed by tyrosine recombinases: Flp H305. Chem Biol. 2007. PubMed, PDB 1M6X
2006
Chen Y, Minasov G, Roth TA, Prati F, Shoichet BK. The deacylation mechanism of AmpC beta-lactamase at ultrahigh resolution. J Am Chem Soc. 2006. PubMed, PDB 2FFY
2005
Chen Y, Shoichet B, Bonnet R. Structure, function, and inhibition along the reaction coordinate of CTX-M beta-lactamases. J Am Chem Soc. 2005. PubMed, PDB 1YLY, 1YLZ, 1YM1, 1YMS, 1YMX
Chen Y, Delmas J, Sirot J, Shoichet B, Bonnet R. Atomic resolution structures of CTX-M beta-lactamases: extended spectrum activities from increased mobility and decreased stability. J Mol Biol. 2005. PubMed, PDB 1YLJ, 1YLP, 1YLT, 1YLW
2003
Chen Y, Rice PA. New insight into site-specific recombination from Flp recombinase-DNA structures. Annu Rev Biophys Biomol Struct. 2003. PubMed
Chen Y, Rice PA. The role of the conserved Trp330 in Flp-mediated recombination. Functional and structural analysis. J Biol Chem. 2003. PubMed
2000
Chen Y, Narendra U, Iype LE, Cox MM, Rice PA. Crystal structure of a Flp recombinase-Holliday junction complex: assembly of an active oligomer by helix swapping. Mol Cell. 2000. PubMed