Publications | Structural Genomics Consortium

Re-evaluating the mechanism of action of α,β-unsaturated carbonyl DUB inhibitors b-AP15 and VLX1570: a paradigmatic example of unspecific protein crosslinking with Michael acceptor motif-containing drugs.

Ward JA, Pinto-Fernandez A, Cornelissen L, Bonham S, Díaz-Sáez L, Riant O, Huber KVM, Kessler BM, Feron O, Tate EW

J. Med. Chem.. doi: 10.1021/acs.jmedchem.0c00144

Publication date: February 28, 2020

Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas.

Fortin J, Tian R, Zarrabi I, Hill G, Williams E, Sanchez-Duffhues G, Thorikay M, Ramachandran P, Siddaway R, Wong JF, Wu A, Apuzzo LN, Haight J, You-Ten A, Snow BE, Wakeham A, Goldhamer DJ, Schramek D, Bullock AN, Dijke PT, Hawkins C, Mak TW

Cancer Cell. doi: 10.1016/j.ccell.2020.02.002

Publication date: February 21, 2020

PMID: 32142668

Structure-based view of the druggable genome.

Wang J, Yazdani S, Han A, Schapira M

Drug Discov. Today. doi: 10.1016/j.drudis.2020.02.006

Publication date: February 19, 2020

PMID: 32084498

Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer.

Scott F, Fala AM, Pennicott LE, Reuillon TD, Massirer KB, Elkins JM, Ward SE

Bioorg. Med. Chem. Lett.. 127040. doi: 10.1016/j.bmcl.2020.127040

Publication date: February 17, 2020

PMID: 32085971

Michelanglo: sculpting protein views on web pages without coding.

Ferla MP, Pagnamenta AT, Damerell D, Taylor JC, Marsden BD

Bioinformatics. doi: 10.1093/bioinformatics/btaa104

Publication date: February 15, 2020

PMID: 32061125

Identification of molecular targets for the targeted treatment of gastric cancer using dasatinib.

Montenegro RC, Howarth A, Ceroni A, Fedele V, Farran B, Mesquita FP, Frejno M, Berger BT, Heinzlmeir S, Sailem HZ, Tesch R, Ebner D, Knapp S, Burbano R, Kuster B, Müller S

Oncotarget. 11(5):535-549. doi: 10.18632/oncotarget.27462

Publication date: February 4, 2020

PMID: 32082487

In vitro benchmarking of NF-κB inhibitors.

Harrold AP, Cleary MM, Bharathy N, Lathara M, Berlow NE, Foreman NK, Donson AM, Amani V, Zuercher WJ, Keller C

Eur. J. Pharmacol.. 172981. doi: 10.1016/j.ejphar.2020.172981

Publication date: January 31, 2020

PMID: 32014486

Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication.

Abeywickrama-Samarakoon N, Cortay JC, Sureau C, Müller S, Alfaiate D, Guerrieri F, Chaikuad A, Schröder M, Merle P, Levrero M, Dény P

Nat Commun. 11(1):419. doi: 10.1038/s41467-020-14299-9

Publication date: January 21, 2020

PMID: 31964889

Bi-allelic Variants in TKFC Encoding Triokinase/FMN Cyclase Are Associated with Cataracts and Multisystem Disease.

Wortmann SB, Meunier B, Mestek-Boukhibar L, van den Broek F, Maldonado EM, Clement E, Weghuber D, Spenger J, Jaros Z, Taha F, Yue WW, Heales SJ, Davison JE, Mayr JA, Rahman S

Am. J. Hum. Genet.. doi: 10.1016/j.ajhg.2020.01.005

Publication date: January 17, 2020

PMID: 32004446

In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory Scaffolds.

O'Byrne SN, Scott JW, Pilotte JR, Santiago ADS, Langendorf CG, Oakhill JS, Eduful BJ, Couñago RM, Wells CI, Zuercher WJ, Willson TM, Drewry DH

Molecules. 25(2):. doi: 10.3390/molecules25020325

Publication date: January 13, 2020

PMID: 31941153

Overcoming Fungal Echinocandin Resistance through Inhibition of the Non-essential Stress Kinase Yck2.

Caplan T, Lorente-Macías Á, Stogios PJ, Evdokimova E, Hyde S, Wellington MA, Liston S, Iyer KR, Puumala E, Shekhar-Guturja T, Robbins N, Savchenko A, Krysan DJ, Whitesell L, Zuercher WJ, Cowen LE

Cell Chem Biol. doi: 10.1016/j.chembiol.2019.12.008

Publication date: January 6, 2020

PMID: 31924499

Effects of epigenetic pathway inhibitors on corticotroph tumour AtT20 cells.

Lines KE, Filippakopoulos P, Stevenson M, Muller S, Lockstone HE, Wright B, Knapp S, Buck D, Bountra C, Thakker RV

Endocr. Relat. Cancer. doi: 10.1530/ERC-19-0448

Publication date: January 1, 2020

PMID: 31935194

Human MettL3-MettL14 complex is a sequence-specific DNA adenine methyltransferase active on single-strand and unpaired DNA in vitro.

Woodcock CB, Yu D, Hajian T, Li J, Huang Y, Dai N, Corrêa IR, Wu T, Vedadi M, Zhang X, Cheng X

Cell Discov. 5:63. doi: 10.1038/s41421-019-0136-4

Publication date: December 31, 2019

PMID: 31885874

The crystal structure of human forkhead box N1 in complex with DNA reveals the structural basis for forkhead box family specificity.

Newman JA, Aitkenhead H, Gavard AE, Rota IA, Handel AE, Hollander GA, Gileadi O

J. Biol. Chem.. doi: 10.1074/jbc.RA119.010365

Publication date: December 30, 2019

PMID: 31914405

Human MettL3-MettL14 complex is a sequence-specific DNA adenine methyltransferase active on single-strand and unpaired DNA in vitro.

Woodcock CB, Yu D, Hajian T, Li J, Huang Y, Dai N, Corrêa IR, Wu T, Vedadi M, Zhang X, Cheng X

Cell Discov. 5(1):63. doi: 10.1038/s41421-019-0136-4

Publication date: December 24, 2019

PMID: 33353928

Discovery of a chemical probe for PRDM9.

Allali-Hassani A, Szewczyk MM, Ivanochko D, Organ SL, Bok J, Ho JSY, Gay FPH, Li F, Blazer L, Eram MS, Halabelian L, Dilworth D, Luciani GM, Lima-Fernandes E, Wu Q, Loppnau P, Palmer N, Talib SZA, Brown PJ, Schapira M, Kaldis P, O'Hagan RC, Guccione E, Barsyte-Lovejoy D, Arrowsmith CH, Sanders JM, Kattar SD, Bennett DJ, Nicholson B, Vedadi M

Nat Commun. 10(1):5759. doi: 10.1038/s41467-019-13652-x

Publication date: December 17, 2019

PMID: 31848333

Structural Insights into Interaction Mechanisms of Alternative Piperazine-urea YEATS Domain Binders in MLLT1.

Ni X, Heidenreich D, Christott T, Bennett J, Moustakim M, Brennan PE, Fedorov O, Knapp S, Chaikuad A

ACS Med Chem Lett. 10(12):1661-1666. doi: 10.1021/acsmedchemlett.9b00460

Publication date: December 12, 2019

PMID: 31857843

Methyltransferase Inhibitors: Competing with, or Exploiting the Bound Cofactor.

Ferreira de Freitas R, Ivanochko D, Schapira M

Molecules. 24(24):. doi: 10.3390/molecules24244492

Publication date: December 8, 2019

PMID: 31817960

Structural consequences of BMPR2 kinase domain mutations causing pulmonary arterial hypertension.

Chaikuad A, Thangaratnarajah C, von Delft F, Bullock AN

Sci Rep. 9(1):18351. doi: 10.1038/s41598-019-54830-7

Publication date: December 4, 2019

PMID: 31797984

Chemical Probes for Protein Arginine Methyltransferases.

Ming Li AS, Li F, Eram MS, Bolotokova A, Dela Seña CC, Vedadi M

Methods. doi: 10.1016/j.ymeth.2019.11.017

Publication date: December 3, 2019

PMID: 31809836

Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers.

Lovejoy DA, Hogg DW, Dodsworth TL, Jurado FR, Read CC, D'Aquila AL, Barsyte-Lovejoy D

Front Endocrinol (Lausanne). 10:730. doi: 10.3389/fendo.2019.00730

Publication date: November 30, 2019

PMID: 31781029

Development of Macrocycle Kinase Inhibitors for ALK2 Using Fibrodysplasia Ossificans Progressiva-Derived Endothelial Cells.

Sánchez-Duffhues G, Williams E, Benderitter P, Orlova V, van Wijhe M, Garcia de Vinuesa A, Kerr G, Caradec J, Lodder K, de Boer HC, Goumans MJ, Eekhoff EMW, Morales-Piga A, Bachiller-Corral J, Koolwijk P, Bullock AN, Hoflack J, Ten Dijke P

JBMR Plus. 3(11):e10230. doi: 10.1002/jbm4.10230

Publication date: November 27, 2019

PMID: 31768489

Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2.

Wang Q, Corey RA, Hedger G, Aryal P, Grieben M, Nasrallah C, Baronina A, Pike ACW, Shi J, Carpenter EP, Sansom MSP

Structure. doi: 10.1016/j.str.2019.11.005

Publication date: November 27, 2019

PMID: 31806353

The fungal metabolite chaetocin is a sensitizer for pro-apoptotic therapies in glioblastoma.

Ozyerli-Goknar E, Sur-Erdem I, Seker F, Cingöz A, Kayabolen A, Kahya-Yesil Z, Uyulur F, Gezen M, Tolay N, Erman B, Gönen M, Dunford J, Oppermann U, Bagci-Onder T

Cell Death Dis. 10(12):894. doi: 10.1038/s41419-019-2107-y

Publication date: November 26, 2019

PMID: 31772153

Janus kinase inhibition for autoinflammation in DNASE2 deficiency.

Hong Y, Capitani M, Murphy C, Pandey S, Cavounidis A, Takeshita H, Nanthapisal S, Yasuda T, Bader-Meunier B, McCreary D, Omoyinmi E, Rao A, Booth C, Gilmour K, Sebire N, Shah N, Klein N, Bullock AN, Eleftheriou D, Uhlig HH, Brogan P

J. Allergy Clin. Immunol.. doi: 10.1016/j.jaci.2019.11.020

Publication date: November 24, 2019

PMID: 31775019

An epigenetic screening determines BET proteins as targets to suppress self-renewal and tumorigenicity in canine mammary cancer cells.

Xavier PLP, Cordeiro YG, Alexandre PA, Pires PRL, Saranholi BH, Silva ER, Müller S, Fukumasu H

Sci Rep. 9(1):17363. doi: 10.1038/s41598-019-53915-7

Publication date: November 22, 2019

PMID: 31758045

HMCES Functions in the Alternative End-Joining Pathway of the DNA DSB Repair during Class Switch Recombination in B Cells.

Shukla V, Halabelian L, Balagere S, Samaniego-Castruita D, Feldman DE, Arrowsmith CH, Rao A, Aravind L

Mol. Cell. doi: 10.1016/j.molcel.2019.10.031

Publication date: November 15, 2019

PMID: 31806351

Binding and structural analyses of potent inhibitors of the human Ca2+/calmodulin dependent protein kinase kinase 2 (CAMKK2) identified from a collection of commercially-available kinase inhibitors.

Profeta GS, Dos Reis CV, Santiago ADS, Godoi PHC, Fala AM, Wells CI, Sartori R, Salmazo APT, Ramos PZ, Massirer KB, Elkins JM, Drewry DH, Gileadi O, Couñago RM

Sci Rep. 9(1):16452. doi: 10.1038/s41598-019-52795-1

Publication date: November 11, 2019

PMID: 31712618

Emerging tools to investigate bromodomain functions.

Kougnassoukou Tchara PE, Filippakopoulos P, Lambert JP

Methods. doi: 10.1016/j.ymeth.2019.11.003

Publication date: November 11, 2019

PMID: 31726225

A fast iterative synthetic approach towards the identification of novel highly selective p38 MAP kinase inhibitors.

Röhm S, Berger BT, Schröder M, Chaikuad A, Winkel R, Hekking KFW, Benningshof JJC, Mueller G, Tesch R, Kudolo M, Forster M, Laufer SA, Knapp S

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b01227

Publication date: November 8, 2019

PMID: 31702918

Towards the Development of an In vivo Chemical Probe for Cyclin G Associated Kinase (GAK).

Asquith CRM, Bennett JM, Su L, Laitinen T, Elkins JM, Pickett JE, Wells CI, Li Z, Willson TM, Zuercher WJ

Molecules. 24(22):. doi: 10.3390/molecules24224016

Publication date: November 6, 2019

PMID: 31698822

Multiple direct interactions of TBP with the MYC oncoprotein.

Wei Y, Resetca D, Li Z, Johansson-Åkhe I, Ahlner A, Helander S, Wallenhammar A, Morad V, Raught B, Wallner B, Kokubo T, Tong Y, Penn LZ, Sunnerhagen M

Nat. Struct. Mol. Biol.. doi: 10.1038/s41594-019-0321-z

Publication date: November 4, 2019

PMID: 31686052

Design and analysis of the 4-anilino-quin(az)oline kinase inhibition profiles of GAK/SLK/STK10 using quantitative structure activity relationships.

Asquith CRM, Laitinen T, Bennett JM, Wells CI, Elkins JM, Zuercher WJ, Tizzard G, Poso A

ChemMedChem. doi: 10.1002/cmdc.201900521

Publication date: November 1, 2019

PMID: 31675459

Discovery of small molecule antagonists of the USP5 zinc finger ubiquitin-binding domain.

Mann MK, Franzoni I, de Freitas RF, Tempel W, Houliston S, Smith L, Vedadi M, Arrowsmith CH, Harding RJ, Schapira M

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b00988

Publication date: October 30, 2019

PMID: 31663737

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

PMID: 31666732

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