Publications | Structural Genomics Consortium

Ferreira IM, Edwin N Quesñay J, Bastos AC, Rodrigues CT, Vollmar M, Krojer T, Strain-Damerell C, Burgess-Brown NA, von Delft F, Yue WW, Dias SM, Ambrosio AL

Biochimie. doi: 10.1016/j.biochi.2021.03.009

Publication date: March 18, 2021

PMID: 33746066

Dissecting the Role of BET Bromodomain Proteins BRD2 and BRD4 in Human NK Cell Function.

Cribbs AP, Filippakopoulos P, Philpott M, Wells G, Penn H, Oerum H, Valge-Archer V, Feldmann M, Oppermann U

Front Immunol. 12:626255. doi: 10.3389/fimmu.2021.626255

Publication date: March 16, 2021

PMID: 33717143

Fragment Screening Reveals Starting Points for Rational Design of Galactokinase 1 Inhibitors to Treat Classic Galactosemia.

Mackinnon SR, Krojer T, Foster WR, Diaz-Saez L, Tang M, Huber KVM, von Delft F, Lai K, Brennan PE, Arruda Bezerra G, Yue WW

ACS Chem Biol. doi: 10.1021/acschembio.0c00498

Publication date: March 16, 2021

PMID: 33724769

Characterization of a natural variant of human NDP52 and its functional consequences on mitophagy.

Di Rita A, Angelini DF, Maiorino T, Caputo V, Cascella R, Kumar M, Tiberti M, Lambrughi M, Wesch N, Löhr F, Dötsch V, Carinci M, D'Acunzo P, Chiurchiù V, Papaleo E, Rogov VV, Giardina E, Battistini L, Strappazzon F

Cell Death Differ. doi: 10.1038/s41418-021-00766-3

Publication date: March 15, 2021

PMID: 33723372

7-(2-Anilinopyrimidin-4-yl)-1-benzazepin-2-ones Designed by a "Cut and Glue" Strategy Are Dual Aurora A/VEGF-R Kinase Inhibitors.

Karatas M, Chaikuad A, Berger B, Kubbutat MHG, Totzke F, Knapp S, Kunick C

Molecules. 26(6):. doi: 10.3390/molecules26061611

Publication date: March 14, 2021

PMID: 33799460

Affinity-matured HLA class II dimers for robust staining of antigen-specific CD4+ T cells.

Sugata K, Matsunaga Y, Yamashita Y, Nakatsugawa M, Guo T, Halabelian L, Ohashi Y, Saso K, Rahman MA, Anczurowski M, Wang CH, Murata K, Saijo H, Kagoya Y, Ly D, Burt BD, Butler MO, Mak TW, Hirano N

Nat Biotechnol. doi: 10.1038/s41587-021-00836-4

Publication date: March 1, 2021

PMID: 33649568

Reply to: Binding site for MDL-801 on SIRT6.

Huang Z, Zhao J, Deng W, Chen Y, Shang J, Song K, Zhang L, Wang C, Lu S, Yang X, He B, Min J, Hu H, Tan M, Xu J, Zhang Q, Zhong J, Sun X, Mao Z, Lin H, Xiao M, Chin YE, Jiang H, Shen H, Xu Y, Chen G, Zhang J

Nat Chem Biol. doi: 10.1038/s41589-021-00750-5

Publication date: March 1, 2021

PMID: 33649600

Probing the SAM Binding Site of SARS-CoV-2 nsp14 in vitro Using SAM Competitive Inhibitors Guides Developing Selective bi-substrate Inhibitors.

Devkota K, Schapira M, Perveen S, Yazdi AK, Li F, Chau I, Ghiabi P, Hajian T, Loppnau P, Bolotokova A, Satchell KJF, Wang K, Li D, Liu J, Smil D, Luo M, Jin J, Fish PV, Brown PJ, Vedadi M

bioRxiv. doi: 10.1101/2021.02.19.424337

Publication date: February 19, 2021

PMID: 33619486

Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core.

Němec V, Maier L, Berger BT, Chaikuad A, Drápela S, Souček K, Knapp S, Paruch K

Eur J Med Chem. 215:113299. doi: 10.1016/j.ejmech.2021.113299

Publication date: February 18, 2021

PMID: 33636538

A First-in-Class, Highly Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 6.

Shen Y, Li F, Szewczyk MM, Halabelian L, Chau I, Eram MS, Dela Seña C, Park KS, Meng F, Chen H, Zeng H, McLeod D, Zepeda-Velázquez CA, Campbell RM, Mader MM, Watson BM, Schapira M, Arrowsmith CH, Al-Awar R, Barsyte-Lovejoy D, Kaniskan HÜ, Brown PJ, Vedadi M, Jin J

J Med Chem. doi: 10.1021/acs.jmedchem.0c02160

Publication date: February 16, 2021

PMID: 33591753

A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation.

Ostrop J, Zwiggelaar RT, Terndrup Pedersen M, Gerbe F, Bösl K, Lindholm HT, Díez-Sánchez A, Parmar N, Radetzki S, von Kries JP, Jay P, Jensen KB, Arrowsmith C, Oudhoff MJ

Front Cell Dev Biol. 8:618552. doi: 10.3389/fcell.2020.618552

Publication date: February 13, 2021

PMID: 33575256

PRMT5 inhibition disrupts splicing and stemness in glioblastoma.

Sachamitr P, Ho JC, Ciamponi FE, Ba-Alawi W, Coutinho FJ, Guilhamon P, Kushida MM, Cavalli FMG, Lee L, Rastegar N, Vu V, Sánchez-Osuna M, Coulombe-Huntington J, Kanshin E, Whetstone H, Durand M, Thibault P, Hart K, Mangos M, Veyhl J, Chen W, Tran N, Duong BC, Aman AM, Che X, Lan X, Whitley O, Zaslaver O, Barsyte-Lovejoy D, Richards LM, Restall I, Caudy A, Röst HL, Bonday ZQ, Bernstein M, Das S, Cusimano MD, Spears J, Bader GD, Pugh TJ, Tyers M, Lupien M, Haibe-Kains B, Artee Luchman H, Weiss S, Massirer KB, Prinos P, Arrowsmith CH, Dirks PB

Nat Commun. 12(1):979. doi: 10.1038/s41467-021-21204-5

Publication date: February 12, 2021

PMID: 33579912

Crystal structure of the BRPF2 PWWP domain in complex with DNA reveals a different binding mode than the HDGF family of PWWP domains.

Zhang M, Lei M, Qin S, Dong A, Yang A, Li Y, Loppnau P, Hughes TR, Min J, Liu Y

Biochim Biophys Acta Gene Regul Mech. 194688. doi: 10.1016/j.bbagrm.2021.194688

Publication date: February 5, 2021

PMID: 33556623

High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging.

Chen J, Sivan U, Tan SL, Lippo L, De Angelis J, Labella R, Singh A, Chatzis A, Cheuk S, Medhghalchi M, Gil J, Hollander G, Marsden BD, Williams R, Ramasamy SK, Kusumbe AP

Sci Adv. 7(6):. doi: 10.1126/sciadv.abd7819

Publication date: February 5, 2021

PMID: 33536212

Discovery of Small-Molecule Antagonists of the PWWP Domain of NSD2.

Ferreira de Freitas R, Liu Y, Szewczyk MM, Mehta N, Li F, McLeod D, Zepeda-Velázquez C, Dilworth D, Hanley RP, Gibson E, Brown PJ, Al-Awar R, James LI, Arrowsmith CH, Barsyte-Lovejoy D, Min J, Vedadi M, Schapira M, Allali-Hassani A

J Med Chem. doi: 10.1021/acs.jmedchem.0c01768

Publication date: February 1, 2021

PMID: 33522809

Rational Design and Synthesis of Selective PRMT4 Inhibitors: a New Chemotype for Development of Cancer Therapeutics.

Santhakumar V, Sutherland M, Li A, Kaghad A, Panagopoulos D, Li F, Szewczyk M, Smil D, Scholten C, Bouché L, Stellfeld T, Arrowsmith CH, Barsyte D, Vedadi M, Hartung IV, Steuber H, Britton R

ChemMedChem. doi: 10.1002/cmdc.202100018

Publication date: January 29, 2021

PMID: 33513288

Drugging the 'undruggable' MYCN oncogenic transcription factor: Overcoming previous obstacles to impact childhood cancers.

Wolpaw AJ, Bayliss R, Büchel G, Dang CV, Eilers M, Gustafson WC, Hansen GM, Jura N, Knapp S, Lemmon MA, Levens D, Maris JM, Marmorstein R, Metallo SJ, Park JR, Penn LZ, Rape M, Roussel MF, Shokat KM, Tansey WP, Verba KA, Vos SM, Weiss WA, Wolf E, Mossé YP

Cancer Res. doi: 10.1158/0008-5472.CAN-20-3108

Publication date: January 28, 2021

PMID: 33509943

Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2.

Berger BT, Amaral M, Kokh DB, Nunes-Alves A, Musil D, Heinrich T, Schröder M, Neil R, Wang J, Navratilova I, Bomke J, Elkins JM, Müller S, Frech M, Wade RC, Knapp S

Cell Chem Biol. doi: 10.1016/j.chembiol.2021.01.003

Publication date: January 21, 2021

PMID: 33497606

Identification of small molecule allosteric modulators of 5,10-methylenetetrahydrofolate reductase (MTHFR) by targeting its unique regulatory domain.

Bezerra GA, Holenstein A, Foster WR, Xie B, Hicks KG, Bürer C, Lutz S, Mukherjee A, Sarkar D, Bhattacharya D, Rutter J, Talukdar A, Brown PJ, Luo M, Shi L, Froese DS, Yue WW

Biochimie. doi: 10.1016/j.biochi.2021.01.007

Publication date: January 18, 2021

PMID: 33476699

Large-scale survey and database of high affinity ligands for peptide recognition modules.

Teyra J, Kelil A, Jain S, Helmy M, Jajodia R, Hooda Y, Gu J, D'Cruz AA, Nicholson SE, Min J, Sudol M, Kim PM, Bader GD, Sidhu SS

Mol Syst Biol. 16(12):e9310. doi: 10.15252/msb.20199310

Publication date: January 14, 2021

PMID: 33438817

BET inhibition disrupts transcription but retains enhancer-promoter contact.

Crump NT, Ballabio E, Godfrey L, Thorne R, Repapi E, Kerry J, Tapia M, Hua P, Lagerholm C, Filippakopoulos P, Davies JOJ, Milne TA

Nat Commun. 12(1):223. doi: 10.1038/s41467-020-20400-z

Publication date: January 11, 2021

PMID: 33431820

Development of a potent and selective chemical probe for the pleiotropic kinase CK2.

Wells CI, Drewry DH, Pickett JE, Tjaden A, Krämer A, Müller S, Gyenis L, Menyhart D, Litchfield DW, Knapp S, Axtman AD

Cell Chem Biol. doi: 10.1016/j.chembiol.2020.12.013

Publication date: January 11, 2021

PMID: 33484635

A High-Throughput RNA Displacement Assay for Screening SARS-CoV-2 nsp10-nsp16 Complex toward Developing Therapeutics for COVID-19.

Perveen S, Khalili Yazdi A, Devkota K, Li F, Ghiabi P, Hajian T, Loppnau P, Bolotokova A, Vedadi M

SLAS Discov. 2472555220985040. doi: 10.1177/2472555220985040

Publication date: January 10, 2021

PMID: 33423577

The Kinase Chemogenomic Set (KCGS): An Open Science Resource for Kinase Vulnerability Identification.

Wells CI, Al-Ali H, Andrews DM, Asquith CRM, Axtman AD, Dikic I, Ebner D, Ettmayer P, Fischer C, Frederiksen M, Futrell RE, Gray NS, Hatch SB, Knapp S, Lücking U, Michaelides M, Mills CE, Müller S, Owen D, Picado A, Saikatendu KS, Schröder M, Stolz A, Tellechea M, Turunen BJ, Vilar S, Wang J, Zuercher WJ, Willson TM, Drewry DH

Int J Mol Sci. 22(2):. doi: 10.3390/ijms22020566

Publication date: January 8, 2021

PMID: 33429995

Molecular basis for ubiquitin ligase CRL2FEM1C-mediated recognition of C-degron.

Yan X, Wang X, Li Y, Zhou M, Li Y, Song L, Mi W, Min J, Dong C

Nat Chem Biol. doi: 10.1038/s41589-020-00703-4

Publication date: January 4, 2021

PMID: 33398170

The low-cost Shifter microscope stage transforms the speed and robustness of protein crystal harvesting.

Wright ND, Collins P, Koekemoer L, Krojer T, Talon R, Nelson E, Ye M, Nowak R, Newman J, Ng JT, Mitrovich N, Wiggers H, von Delft F

Acta Crystallogr D Struct Biol. 77(Pt 1):62-74. doi: 10.1107/S2059798320014114

Publication date: January 1, 2021

PMID: 33404526

Towards a RIOK2 chemical probe: cellular potency improvement of a selective 2-(acylamino)pyridine series.

Wang CB, Lorente-Macías Á, Wells C, Pickett JE, Picado A, Zuercher WJ, Axtman AD

RSC Med Chem. 12(1):129-136. doi: 10.1039/d0md00292e

Publication date: January 1, 2021

PMID: 34046605

Inhibition of the SUV4-20 H1 histone methyltransferase increases frataxin expression in Friedreich's ataxia patient cells.

Vilema-Enríquez G, Quinlan R, Kilfeather P, Mazzone R, Saqlain S, Del Molino Del Barrio I, Donato A, Corda G, Li F, Vedadi M, Németh AH, Brennan PE, Wade-Martins R

J Biol Chem. 295(52):17973-17985. doi: 10.1074/jbc.RA120.015533

Publication date: December 25, 2020

PMID: 33453810

How to Separate Kinase Inhibition from Undesired Monoamine Oxidase A Inhibition-The Development of the DYRK1A Inhibitor AnnH75 from the Alkaloid Harmine.

Wurzlbauer A, Rüben K, Gürdal E, Chaikuad A, Knapp S, Sippl W, Becker W, Bracher F

Molecules. 25(24):. doi: 10.3390/molecules25245962

Publication date: December 16, 2020

PMID: 33339338

Identification of lysine isobutyrylation as a new histone modification mark.

Zhu Z, Han Z, Halabelian L, Yang X, Ding J, Zhang N, Ngo L, Song J, Zeng H, He M, Zhao Y, Arrowsmith CH, Luo M, Bartlett MG, Zheng YG

Nucleic Acids Res. doi: 10.1093/nar/gkaa1176

Publication date: December 11, 2020

PMID: 33313896

Pan-SMARCA/PB1 Bromodomain Inhibitors and Their Role in Regulating Adipogenesis.

Wanior M, Preuss F, Ni X, Krämer A, Mathea S, Göbel T, Heidenreich D, Simonyi S, Kahnt AS, Joerger AC, Knapp S

J Med Chem. 63(23):14680-14699. doi: 10.1021/acs.jmedchem.0c01242

Publication date: December 10, 2020

PMID: 33216538

Discovery of a Novel Class of Covalent Dual Inhibitors Targeting the Protein Kinases BMX and BTK.

Forster M, Liang XJ, Schröder M, Gerstenecker S, Chaikuad A, Knapp S, Laufer S, Gehringer M

Int J Mol Sci. 21(23):. doi: 10.3390/ijms21239269

Publication date: December 4, 2020

PMID: 33291717

Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene.

Doffe F, Carbonnier V, Tissier M, Leroy B, Martins I, Mattsson JSM, Micke P, Pavlova S, Pospisilova S, Smardova J, Joerger AC, Wiman KG, Kroemer G, Soussi T

Cell Death Differ. 28(5):1477-1492. doi: 10.1038/s41418-020-00672-0

Publication date: December 2, 2020

PMID: 33257846

BETs inhibition attenuates oxidative stress and preserves muscle integrity in Duchenne muscular dystrophy.

Segatto M, Szokoll R, Fittipaldi R, Bottino C, Nevi L, Mamchaoui K, Filippakopoulos P, Caretti G

Nat Commun. 11(1):6108. doi: 10.1038/s41467-020-19839-x

Publication date: November 30, 2020

PMID: 33257646

A Single-Stranded DNA-Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks.

Bassi G, Favalli N, Vuk M, Catalano M, Martinelli A, Trenner A, Porro A, Yang S, Tham CL, Moroglu M, Yue WW, Conway SJ, Vogt PK, Sartori AA, Scheuermann J, Neri D

Adv Sci (Weinh). 7(22):2001970. doi: 10.1002/advs.202001970

Publication date: November 27, 2020

PMID: 33240760

Fragment Binding to the Nsp3 Macrodomain of SARS-CoV-2 Identified Through Crystallographic Screening and Computational Docking.

Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, Young ID, Martins LC, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT, Aimon A, Bennett JM, Neto JB, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs M, Gorrie-Stone TJ, Holton JM, Johnson MG, Krojer T, Meigs G, Powell AJ, Rack JGM, Rangel VL, Russi S, Skyner RE, Smith CA, Soares AS, Wierman JL, Zhu K, Jura N, Ashworth A, Irwin J, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I

bioRxiv. doi: 10.1101/2020.11.24.393405

Publication date: November 24, 2020

PMID: 33269349

A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation.

Picado A, Chaikuad A, Wells CI, Shrestha S, Zuercher WJ, Pickett JE, Kwarcinski FE, Sinha P, de Silva CS, Zutshi R, Liu S, Kannan N, Knapp S, Drewry DH, Willson TM

J Med Chem. doi: 10.1021/acs.jmedchem.0c01174

Publication date: November 20, 2020

PMID: 33215924