Publications | Structural Genomics Consortium

Targeted protein degradation: expanding the toolbox.

Schapira M, Calabrese MF, Bullock AN, Crews CM

Nat Rev Drug Discov. doi: 10.1038/s41573-019-0047-y

Publication date: October 30, 2019

A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion.

Cai XC, Zhang T, Kim EJ, Jiang M, Wang K, Wang J, Chen S, Zhang N, Wu H, Li F, Dela Seña CC, Zeng H, Vivcharuk V, Niu X, Zheng W, Lee JP, Chen Y, Barsyte D, Szewczyk M, Hajian T, Ibáñez G, Dong A, Dombrovski L, Zhang Z, Deng H, Min J, Arrowsmith CH, Mazutis L, Shi L, Vedadi M, Brown PJ, Xiang J, Qin LX, Xu W, Luo M

Elife. 8:. doi: 10.7554/eLife.47110

Publication date: October 28, 2019

PMID: 31657716

Aspartate/asparagine-β-hydroxylase crystal structures reveal an unexpected epidermal growth factor-like domain substrate disulfide pattern.

Pfeffer I, Brewitz L, Krojer T, Jensen SA, Kochan GT, Kershaw NJ, Hewitson KS, McNeill LA, Kramer H, Münzel M, Hopkinson RJ, Oppermann U, Handford PA, McDonough MA, Schofield CJ

Nat Commun. 10(1):4910. doi: 10.1038/s41467-019-12711-7

Publication date: October 28, 2019

PMID: 31659163

A structure-guided molecular chaperone approach for restoring the transcriptional activity of the p53 cancer mutant Y220C.

Bauer MR, Jones RN, Tareque RK, Springett B, Dingler FA, Verduci L, Patel KJ, Fersht AR, Joerger AC, Spencer J

Future Med Chem. 11(19):2491-2504. doi: 10.4155/fmc-2019-0181

Publication date: October 22, 2019

PMID: 31633398

The C-Terminal Domains SnRK2 Box and ABA Box Have a Role in Sugarcane SnRK2s Auto-Activation and Activity.

Righetto GL, Sriranganadane D, Halabelian L, Chiodi CG, Elkins JM, Massirer KB, Gileadi O, Menossi M, Couñago RM

Front Plant Sci. 10:1105. doi: 10.3389/fpls.2019.01105

Publication date: October 18, 2019

PMID: 31620147

Implementation of an antibody characterization procedure and application to the major ALS/FTD disease gene C9ORF72.

Laflamme C, McKeever PM, Kumar R, Schwartz J, Kolahdouzan M, Chen CX, You Z, Benaliouad F, Gileadi O, McBride HM, Durcan TM, Edwards AM, Healy LM, Robertson J, McPherson PS

Elife. 8:. doi: 10.7554/eLife.48363

Publication date: October 15, 2019

PMID: 31612854

Structural basis for the recognition of non-methylated DNA by the CXXC domain.

Liu K, Min J

J. Mol. Biol.. doi: 10.1016/j.jmb.2019.09.025

Publication date: October 15, 2019

PMID: 31626811

Lessons from LIMK1 enzymology and their impact on inhibitor design.

Salah E, Chatterjee D, Beltrami A, Tumber A, Preuss F, Canning P, Chaikuad A, Knaus P, Knapp S, Bullock AN, Mathea S

Biochem. J.. doi: 10.1042/BCJ20190517

Publication date: October 14, 2019

PMID: 31652302

Quinazoline-based anti-virulence compounds selectively target Salmonella PhoP/PhoQ signal transduction system.

Carabajal MA, Asquith CRM, Laitinen T, Tizzard GJ, Yim L, Rial A, Chabalgoity JA, Zuercher WJ, García Véscovi E

Antimicrob. Agents Chemother.. doi: 10.1128/AAC.01744-19

Publication date: October 14, 2019

PMID: 31611347

Targeting non-bromodomain chromatin readers.

Arrowsmith CH, Schapira M

Nat. Struct. Mol. Biol.. 26(10):863-869. doi: 10.1038/s41594-019-0290-2

Publication date: October 5, 2019

PMID: 31582844

Cryo-EM structures of the human glutamine transporter SLC1A5 (ASCT2) in the outward-facing conformation.

Yu X, Plotnikova O, Bonin PD, Subashi TA, McLellan TJ, Dumlao D, Che Y, Dong YY, Carpenter EP, West GM, Qiu X, Culp JS, Han S

Elife. 8:. doi: 10.7554/eLife.48120

Publication date: October 3, 2019

PMID: 31580259

SETD7 at the heart of chromatin factor interplay.

Barsyte-Lovejoy D

Stem Cell Investig. 6:20. doi: 10.21037/sci.2019.06.01

Publication date: September 29, 2019

PMID: 31559307

A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function.

Fagan V, Johansson C, Gileadi C, Monteiro O, Dunford JE, Nibhani R, Philpott M, Malzahn J, Wells G, Farham R, Cribbs A, Halidi N, Li F, Chau I, Greschik H, Velupillai S, Allali-Hassani A, Bennett JM, Christott T, Giroud C, Lewis AM, Huber KVM, Athanasou N, Bountra C, Jung M, Schüle R, Vedadi M, Arrowsmith CH, Xiong Y, Jin J, Fedorov O, Farnie G, Brennan PE, Oppermann UCT

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b00562

Publication date: September 24, 2019

PMID: 31550156

Fostering open collaboration in drug development for paediatric brain tumours.

Wong JF, Brown EJ, Williams E, Bullock AN

Biochem. Soc. Trans.. doi: 10.1042/BST20190315

Publication date: September 24, 2019

PMID: 31551357

Regulation of DGKε Activity and Substrate Acyl Chain Specificity by Negatively Charged Phospholipids.

Bozelli JC, Yune J, Hou YH, Chatha P, Fernandes A, Cao Z, Tong Y, Epand RM

Biophys. J.. doi: 10.1016/j.bpj.2019.09.008

Publication date: September 16, 2019

PMID: 31587830

Development of Pyridine-based Inhibitors for the Human Vaccinia-related Kinases 1 and 2.

Serafim RAM, de Souza Gama FH, Dutra LA, Dos Reis CV, Vasconcelos SNS, da Silva Santiago A, Takarada JE, Di Pillo F, Azevedo H, Mascarello A, Elkins JM, Massirer KB, Gileadi O, Guimarães CRW, Couñago RM

ACS Med Chem Lett. 10(9):1266-1271. doi: 10.1021/acsmedchemlett.9b00082

Publication date: September 12, 2019

PMID: 31531195

LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA.

Izumikawa K, Ishikawa H, Yoshikawa H, Fujiyama S, Watanabe A, Aburatani H, Tachikawa H, Hayano T, Miura Y, Isobe T, Simpson RJ, Li L, Min J, Takahashi N

Nucleic Acids Res.. doi: 10.1093/nar/gkz747

Publication date: September 2, 2019

PMID: 31504794

The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K.

Bushell SR, Pike ACW, Falzone ME, Rorsman NJG, Ta CM, Corey RA, Newport TD, Christianson JC, Scofano LF, Shintre CA, Tessitore A, Chu A, Wang Q, Shrestha L, Mukhopadhyay SMM, Love JD, Burgess-Brown NA, Sitsapesan R, Stansfeld PJ, Huiskonen JT, Tammaro P, Accardi A, Carpenter EP

Nat Commun. 10(1):3956. doi: 10.1038/s41467-019-11753-1

Publication date: September 2, 2019

PMID: 31477691

Validation of the protein kinase PfCLK3 as a multistage cross-species malarial drug target.

Alam MM, Sanchez-Azqueta A, Janha O, Flannery EL, Mahindra A, Mapesa K, Char AB, Sriranganadane D, Brancucci NMB, Antonova-Koch Y, Crouch K, Simwela NV, Millar SB, Akinwale J, Mitcheson D, Solyakov L, Dudek K, Jones C, Zapatero C, Doerig C, Nwakanma DC, Vázquez MJ, Colmenarejo G, Lafuente-Monasterio MJ, Leon ML, Godoi PHC, Elkins JM, Waters AP, Jamieson AG, Álvaro EF, Ranford-Cartwright LC, Marti M, Winzeler EA, Gamo FJ, Tobin AB

Science. 365(6456):. doi: 10.1126/science.aau1682

Publication date: August 30, 2019

PMID: 31467193

The natural history of infantile mitochondrial DNA depletion syndrome due to RRM2B deficiency.

Keshavan N, Abdenur J, Anderson G, Assouline Z, Barcia G, Bouhikbar L, Chakrapani A, Cleary M, Cohen MC, Feillet F, Fratter C, Hauser N, Jacques T, Lam A, McCullagh H, Phadke R, Rötig A, Sharrard M, Simon M, Smith C, Sommerville EW, Taylor RW, Yue WW, Rahman S

Genet. Med.. doi: 10.1038/s41436-019-0613-z

Publication date: August 29, 2019

PMID: 31462754

Modular Synthesis of Di- and Tri-substituted Imidazoles from Ketones and Aldehydes: A Route to Kinase Inhibitors.

Toledo I, Grigolo TA, Bennett JM, Elkins JM, Pilli RA

J. Org. Chem.. doi: 10.1021/acs.joc.9b01844

Publication date: August 28, 2019

PMID: 31460764

Open laboratory notebooks: good for science, good for society, good for scientists.

Schapira M, Harding RJ

F1000Res. 8:87. doi: 10.12688/f1000research.17710.1

Publication date: August 27, 2019

PMID: 31448096

Target highlights in CASP13: experimental target structures through the eyes of their authors.

Lepore R, Kryshtafovych A, Alahuhta M, Arora Veraszto H, Bomble YJ, Bufton JC, Bullock AN, Caba C, Cao H, Davies OR, Desfosses A, Dunne M, Fidelis K, Goulding CW, Gurusaran M, Gutsche I, Harding CJ, Hartmann MD, Hayes CS, Joachimiak A, Leiman PG, Loppnau P, Lovering AL, Lunin VV, Michalska K, Mir-Sanchis I, Mitra A, Moult J, Phillips GN, Pinkas DM, Rice PA, Tong Y, Topf M, Walton JD, Schwede T

Proteins. doi: 10.1002/prot.25805

Publication date: August 23, 2019

PMID: 31442339

Discovery of first in vivo active inhibitors of soluble epoxide hydrolase (sEH) phosphatase domain.

Kramer JS, Woltersdorf S, Duflot T, Hiesinger K, Lillich FF, Knöll F, Wittmann SK, Klingler FM, Brunst S, Chaikuad A, Morisseau C, Hammock BD, Buccellati C, Sala A, Rovati GE, Leuillier M, Fraineau S, Rondeaux J, Hernandez Olmos V, Heering J, Merk D, Pogoryelov D, Steinhilber D, Knapp S, Bellien J, Proschak E

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b00445

Publication date: August 22, 2019

PMID: 31436984

E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition.

Burdova K, Yang H, Faedda R, Hume S, Chauhan J, Ebner D, Kessler BM, Vendrell I, Drewry DH, Wells CI, Hatch SB, Dianov GL, Buffa FM, D'Angiolella V

EMBO J.. e101443. doi: 10.15252/embj.2018101443

Publication date: August 19, 2019

PMID: 31424118

Targeting an EGFR water network using novel 4-anilinoquin(az)olines inhibitors for chordoma.

Asquith CRM, Maffuid KA, Laitinen T, Torrice C, Tizzard GJ, Crona DJ, Zuercher WJ

ChemMedChem. doi: 10.1002/cmdc.201900428

Publication date: August 19, 2019

PMID: 31424613

Selective, small molecule co-factor binding site inhibition of a Su(var)3-9, Enhancer of Zeste, Trithorax (SET) domain containing lysine methyltransferase.

Taylor AP, Szewczyk MM, Kennedy S, Trush VV, Wu H, Zeng H, Dong A, de Freitas RF, Tatlock JH, Kumpf RA, Wythes M, Casimiro-Garcia A, Denny RA, Parikh MD, Li F, Barsyte-Lovejoy D, Schapira M, Vedadi M, Brown P, Arrowsmith CH, Owen DR

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b00112

Publication date: August 15, 2019

PMID: 31415173

Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation.

Fong JY, Pignata L, Goy PA, Kawabata KC, Lee SC, Koh CM, Musiani D, Massignani E, Kotini AG, Penson A, Wun CM, Shen Y, Schwarz M, Low DH, Rialdi A, Ki M, Wollmann H, Mzoughi S, Gay F, Thompson C, Hart T, Barbash O, Luciani GM, Szewczyk MM, Wouters BJ, Delwel R, Papapetrou EP, Barsyte-Lovejoy D, Arrowsmith CH, Minden MD, Jin J, Melnick A, Bonaldi T, Abdel-Wahab O, Guccione E

Cancer Cell. 36(2):194-209.e9. doi: 10.1016/j.ccell.2019.07.003

Publication date: August 12, 2019

PMID: 31408619

The MLL1 trimeric catalytic complex is a dynamic conformational ensemble stabilized by multiple weak interactions.

Kaustov L, Lemak A, Wu H, Faini M, Fan L, Fang X, Zeng H, Duan S, Allali-Hassani A, Li F, Wei Y, Vedadi M, Aebersold R, Wang Y, Houliston S, Arrowsmith CH

Nucleic Acids Res.. doi: 10.1093/nar/gkz697

Publication date: August 10, 2019

PMID: 31400120

Evaluation of linker length effects on a BET bromodomain probe.

Traquete R, Henderson E, Picaud S, Cal PMSD, Sieglitz F, Rodrigues T, Oliveira R, Filippakopoulos P, Bernardes GJL

Chem. Commun. (Camb.). doi: 10.1039/c9cc05054j

Publication date: August 6, 2019

PMID: 31386708

RIOK2: straddling the kinase/ATPase line.

Asquith CRM, East MP, Zuercher WJ

Nat Rev Drug Discov. 18(8):574. doi: 10.1038/d41573-019-00107-7

Publication date: August 2, 2019

PMID: 31367048

Plasticity at the DNA recognition site of the MeCP2 mCG-binding domain.

Lei M, Tempel W, Chen S, Liu K, Min J

Biochim Biophys Acta Gene Regul Mech. 194409. doi: 10.1016/j.bbagrm.2019.194409

Publication date: July 26, 2019

PMID: 31356990

Structural mechanism of synergistic activation of Aurora kinase B/C by phosphorylated INCENP.

Abdul Azeez KR, Chatterjee S, Yu C, Golub TR, Sobott F, Elkins JM

Nat Commun. 10(1):3166. doi: 10.1038/s41467-019-11085-0

Publication date: July 18, 2019

PMID: 31320618

2-Amino-2, 3-Dihydro-1H-Indene-5-Carboxamide-Based Discoidin Domain Receptors 1 (DDR1) Inhibitors: Design, Synthesis, and In Vivo Anti-pancreatic Cancer Efficacy.

Zhu D, Huang H, Pinkas D, Luo J, Ganguly D, Fox AE, Arner E, Xiang Q, Tu ZC, Bullock AN, Brekken RA, Ding K, Lu X

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b00365

Publication date: July 16, 2019

PMID: 31310125

Identification and characterization of the first fragment hits for SETDB1 Tudor domain.

Mader P, Mendoza-Sanchez R, Iqbal A, Dong A, Dobrovetsky E, Corless VB, Liew SK, Houliston SR, De Freitas RF, Smil D, Sena CCD, Kennedy S, Diaz DB, Wu H, Dombrovski L, Allali-Hassani A, Min J, Schapira M, Vedadi M, Brown PJ, Santhakumar V, Yudin AK, Arrowsmith CH

Bioorg. Med. Chem.. doi: 10.1016/j.bmc.2019.07.020

Publication date: July 12, 2019

PMID: 31327677

Anti-tubercular activity of novel 4-anilinoquinolines and 4-anilinoquinazolines.

Asquith CRM, Fleck N, Torrice CD, Crona DJ, Grundner C, Zuercher WJ

Bioorg. Med. Chem. Lett.. doi: 10.1016/j.bmcl.2019.07.012

Publication date: July 10, 2019

PMID: 31378571

Gram-scale synthesis of FICZ, a photoreactive endogenous ligand of the aryl hydrocarbon receptor.

Zhang C, Creech KL, Zuercher WJ, Willson TM

Sci Rep. 9(1):9982. doi: 10.1038/s41598-019-46374-7

Publication date: July 10, 2019

PMID: 31292477

Mechanisms of Progression of Myeloid Preleukemia to Transformed Myeloid Leukemia in Children with Down Syndrome.

Labuhn M, Perkins K, Matzk S, Varghese L, Garnett C, Papaemmanuil E, Metzner M, Kennedy A, Amstislavskiy V, Risch T, Bhayadia R, Samulowski D, Hernandez DC, Stoilova B, Iotchkova V, Oppermann U, Scheer C, Yoshida K, Schwarzer A, Taub J, Crispino JD, Weiss MJ, Hayashi A, Taga T, Ito E, Ogawa S, Reinhardt D, Yaspo ML, Campbell PJ, Roberts I, Constantinescu S, Vyas P, Heckl D, Klusmann JH

Cancer Cell. doi: 10.1016/j.ccell.2019.06.007

Publication date: July 9, 2019

PMID: 31303423

A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor.

Sin-Chan P, Mumal I, Suwal T, Ho B, Fan X, Singh I, Du Y, Lu M, Patel N, Torchia J, Popovski D, Fouladi M, Guilhamon P, Hansford JR, Leary S, Hoffman LM, Mulcahy Levy JM, Lassaletta A, Solano-Paez P, Rivas E, Reddy A, Gillespie GY, Gupta N, Van Meter TE, Nakamura H, Wong TT, Ra YS, Kim SK, Massimi L, Grundy RG, Fangusaro J, Johnston D, Chan J, Lafay-Cousin L, Hwang EI, Wang Y, Catchpoole D, Michaud J, Ellezam B, Ramanujachar R, Lindsay H, Taylor MD, Hawkins CE, Bouffet E, Jabado N, Singh SK, Kleinman CL, Barsyte-Lovejoy D, Li XN, Dirks PB, Lin CY, Mack SC, Rich JN, Huang A

Cancer Cell. 36(1):51-67.e7. doi: 10.1016/j.ccell.2019.06.002

Publication date: July 8, 2019

PMID: 31287992

Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3.

Böttcher J, Dilworth D, Reiser U, Neumüller RA, Schleicher M, Petronczki M, Zeeb M, Mischerikow N, Allali-Hassani A, Szewczyk MM, Li F, Kennedy S, Vedadi M, Barsyte-Lovejoy D, Brown PJ, Huber KVM, Rogers CM, Wells CI, Fedorov O, Rumpel K, Zoephel A, Mayer M, Wunberg T, Böse D, Zahn S, Arnhof H, Berger H, Reiser C, Hörmann A, Krammer T, Corcokovic M, Sharps B, Winkler S, Häring D, Cockcroft XL, Fuchs JE, Müllauer B, Weiss-Puxbaum A, Gerstberger T, Boehmelt G, Vakoc CR, Arrowsmith CH, Pearson M, McConnell DB

Nat. Chem. Biol.. doi: 10.1038/s41589-019-0310-x

Publication date: July 8, 2019

PMID: 31285596

Lesson from a Fab-enabled co-crystallization study of TDRD2 and PIWIL1.

Chen S, Zhang W, Min J, Liu K

Methods. doi: 10.1016/j.ymeth.2019.07.002

Publication date: July 6, 2019

PMID: 31288074

CDK16: the pick of the understudied PCTAIRE kinases.

Axtman A, Drewry D, Wells C

Nat Rev Drug Discov. 18(7):489. doi: 10.1038/d41573-019-00076-x

Publication date: July 4, 2019

PMID: 31267068

High-Throughput Purification of Protein Kinases from Escherichia coli and Insect Cells.

Mathea S, Salah E, Knapp S

Methods Mol. Biol.. 2025:191-202. doi: 10.1007/978-1-4939-9624-7_8

Publication date: July 4, 2019

PMID: 31267453

High-Throughput Site-Directed Mutagenesis.

Strain-Damerell C, Burgess-Brown NA

Methods Mol. Biol.. 2025:281-296. doi: 10.1007/978-1-4939-9624-7_13

Publication date: July 4, 2019

PMID: 31267458

Target 2035: probing the human proteome.

Carter AJ, Kraemer O, Zwick M, Mueller-Fahrnow A, Arrowsmith CH, Edwards AM

Drug Discov. Today. doi: 10.1016/j.drudis.2019.06.020

Publication date: July 3, 2019

PMID: 31278990

Structural Basis for Recruitment of DAPK1 to the KLHL20 E3 Ligase.

Chen Z, Picaud S, Filippakopoulos P, D'Angiolella V, Bullock AN

Structure. doi: 10.1016/j.str.2019.06.005

Publication date: July 2, 2019

PMID: 31279627

Discovery of a Potent and Selective Fragment-like Inhibitor of Methyllysine Reader Protein Spindlin 1 (SPIN1).

Xiong Y, Greschik H, Johansson C, Seifert L, Bacher J, Park KS, Babault N, Martini ML, Fagan V, Li F, Chau I, Christott T, Dilworth D, Barsyte-Lovejoy D, Vedadi M, Arrowsmith CH, Brennan PE, Fedorov O, Jung M, Farnie G, Liu J, Oppermann UCT, Schüle R, Jin J

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b00522

Publication date: July 1, 2019

PMID: 31260300

A genetics-led approach defines the drug target landscape of 30 immune-related traits.

Fang H, De Wolf H, Knezevic B, Burnham KL, Osgood J, Sanniti A, Lledó Lara A, Kasela S, De Cesco S, Wegner JK, Handunnetthi L, McCann FE, Chen L, Sekine T, Brennan PE, Marsden BD, Damerell D, O'Callaghan CA, Bountra C, Bowness P, Sundström Y, Milani L, Berg L, Göhlmann HW, Peeters PJ, Fairfax BP, Sundström M, Knight JC

Nat. Genet.. doi: 10.1038/s41588-019-0456-1

Publication date: June 28, 2019

PMID: 31253980

Streamlining the production of proteins for structural biology.

Owens RJ, Gileadi O

Biophys Rev. doi: 10.1007/s12551-019-00565-8

Publication date: June 27, 2019

PMID: 31250316

Structures of the cGMP-dependent protein kinase in malaria parasites reveal a unique structural relay mechanism for activation.

El Bakkouri M, Kouidmi I, Wernimont AK, Amani M, Hutchinson A, Loppnau P, Kim JJ, Flueck C, Walker JR, Seitova A, Senisterra G, Kakihara Y, Kim C, Blackman MJ, Calmettes C, Baker DA, Hui R

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1905558116

Publication date: June 25, 2019

PMID: 31239348