Publications | Structural Genomics Consortium

The C-terminal extension landscape of naturally presented HLA-I ligands.

Guillaume P, Picaud S, Baumgaertner P, Montandon N, Schmidt J, Speiser DE, Coukos G, Bassani-Sternberg M, Filippakopoulos P, Gfeller D

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1717277115

Publication date: April 30, 2018

PMID: 29712860

Donated chemical probes for open science.

Müller S, Ackloo S, Arrowsmith CH, Bauser M, Baryza JL, Blagg J, Böttcher J, Bountra C, Brown PJ, Bunnage ME, Carter AJ, Damerell D, Dötsch V, Drewry DH, Edwards AM, Edwards J, Elkins JM, Fischer C, Frye SV, Gollner A, Grimshaw CE, IJzerman A, Hanke T, Hartung IV, Hitchcock S, Howe T, Hughes TV, Laufer S, Li VM, Liras S, Marsden BD, Matsui H, Mathias J, O'Hagan RC, Owen DR, Pande V, Rauh D, Rosenberg SH, Roth BL, Schneider NS, Scholten C, Singh Saikatendu K, Simeonov A, Takizawa M, Tse C, Thompson PR, Treiber DK, Viana AY, Wells CI, Willson TM, Zuercher WJ, Knapp S, Mueller-Fahrnow A

Elife. 7:. doi: 10.7554/eLife.34311

Publication date: April 20, 2018

PMID: 29676732

Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila.

Valleau D, Quaile AT, Cui H, Xu X, Evdokimova E, Chang C, Cuff ME, Urbanus ML, Houliston S, Arrowsmith CH, Ensminger AW, Savchenko A

Cell Rep. 23(2):568-583. doi: 10.1016/j.celrep.2018.03.060

Publication date: April 10, 2018

PMID: 29642013

Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end rule pathway.

Dong C, Zhang H, Li L, Tempel W, Loppnau P, Min J

Nat. Chem. Biol.. doi: 10.1038/s41589-018-0036-1

Publication date: April 9, 2018

PMID: 29632410

A novel INS mutation in a family with MODY: variable insulin secretion and putative mechanisms.

Johnson SR, McGown I, Oppermann U, Conwell LS, Harris M, Duncan EL

Pediatr Diabetes. doi: 10.1111/pedi.12679

Publication date: April 6, 2018

PMID: 29633446

Proteostasis in Huntington's disease: disease mechanisms and therapeutic opportunities.

Harding RJ, Tong YF

Acta Pharmacol Sin. 39(5):754-769. doi: 10.1038/aps.2018.11

Publication date: April 6, 2018

PMID: 29620053

TP-064, a potent and selective small molecule inhibitor of PRMT4 for multiple myeloma.

Nakayama K, Szewczyk MM, Dela Sena C, Wu H, Dong A, Zeng H, Li F, de Freitas RF, Eram MS, Schapira M, Baba Y, Kunitomo M, Cary DR, Tawada M, Ohashi A, Imaeda Y, Saikatendu KS, Grimshaw CE, Vedadi M, Arrowsmith CH, Barsyte-Lovejoy D, Kiba A, Tomita D, Brown PJ

Oncotarget. 9(26):18480-18493. doi: 10.18632/oncotarget.24883

Publication date: April 6, 2018

PMID: 29719619

Large-scale analysis of water stability in bromodomain binding pockets with grand canonical Monte Carlo.

Aldeghi M, Ross GA, Bodkin MJ, Essex JW, Knapp S, Biggin PC

Commun Chem. 1:. doi: 10.1038/s42004-018-0019-x

Publication date: April 5, 2018

PMID: 29863194

A Pseudo-Kinase Double Act.

Preuß F, Mathea S, Knapp S

Structure. 26(4):527-528. doi: 10.1016/j.str.2018.03.008

Publication date: April 3, 2018

PMID: 29617648

Halogen-aromatic π-interactions modulate inhibitor residence time.

Heroven C, Georgi V, Ganotra GK, Brennan PE, Wolfreys F, Wade RC, Fernández-Montalván AE, Chaikuad A, Knapp S

Angew. Chem. Int. Ed. Engl.. doi: 10.1002/anie.201801666

Publication date: March 30, 2018

PMID: 29601130

Identifying small molecule binding sites for epigenetic proteins at domain-domain interfaces.

Brennan P, Bowkett D, Talon R, Tallant C, Schofield C, Bruton G, von Delft F, Knapp S

ChemMedChem. doi: 10.1002/cmdc.201800030

Publication date: March 26, 2018

PMID: 29578648

Therapeutics discovery: From bench to first in-human trials.

Al-Hujaily EM, Khatlani T, Alehaideb Z, Ali R, Almuzaini B, Alrfaei BM, Iqbal J, Islam I, Malik S, Marwani BA, Massadeh S, Nehdi A, Alsomaie B, Debasi B, Bushnak I, Noibi S, Hussain S, Wajid WA, Armand JP, Gul S, Oyarzabal J, Rais R, Bountra C, Alaskar A, Knawy BA, Boudjelal M

Biomed Rep. 8(3):275-282. doi: 10.3892/br.2018.1052

Publication date: March 23, 2018

PMID: 29564125

Structural basis for the ability of MBD domains to bind methyl-CG and TG sites in DNA.

Liu K, Xu C, Lei M, Yang A, Loppnau P, Hughes TR, Min J

J. Biol. Chem.. doi: 10.1074/jbc.RA118.001785

Publication date: March 22, 2018

PMID: 29567833

Structural and functional analysis of the DOT1L-AF10 complex reveals mechanistic insights into MLL-AF10-associated leukemogenesis.

Zhang H, Zhou B, Qin S, Xu J, Harding R, Tempel W, Nayak V, Li Y, Loppnau P, Dou Y, Min J

Genes Dev.. doi: 10.1101/gad.311639.118

Publication date: March 21, 2018

PMID: 29563185

Quantitative characterization of bivalent probes for a dual bromodomain protein, Transcription Initiation Factor TFIID subunit 1, TAF1.

Suh JL, Watts B, Stuckey JI, Norris-Drouin JL, Cholensky SH, Dickson BM, An Y, Mathea S, Salah E, Knapp S, Khan A, Adams AT, Strahl BD, Sagum CA, Bedford MT, James LI, Kireev DB, Frye SV

Biochemistry. doi: 10.1021/acs.biochem.8b00150

Publication date: March 20, 2018

PMID: 29558110

New opportunities for kinase drug repurposing and target discovery.

Knapp S

Br. J. Cancer. doi: 10.1038/s41416-018-0045-6

Publication date: March 16, 2018

PMID: 29545596

Effects of FKBP12 and type II BMP receptors on signal transduction by ALK2 activating mutations associated with genetic disorders.

Machiya A, Tsukamoto S, Ohte S, Kuratani M, Fujimoto M, Kumagai K, Osawa K, Suda N, Bullock AN, Katagiri T

Bone. doi: 10.1016/j.bone.2018.03.015

Publication date: March 15, 2018

PMID: 29551750

Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation.

Pariollaud M, Gibbs J, Hopwood T, Brown S, Begley N, Vonslow R, Poolman T, Guo B, Saer B, Jones DH, Tellam JP, Bresciani S, Tomkinson NC, Wojno-Picon J, Cooper AW, Daniels DA, Trump RP, Grant D, Zuercher W, Willson TM, MacDonald AS, Bolognese B, Podolin PL, Sanchez Y, Loudon AS, Ray DW

J. Clin. Invest.. doi: 10.1172/JCI93910

Publication date: March 13, 2018

PMID: 29533925

Discovery of a novel allosteric inhibitor scaffold for polyadenosine-diphosphate-ribose polymerase 14 (PARP14) macrodomain 2.

Moustakim M, Riedel K, Schuller M, Gehring AP, Monteiro OP, Martin SP, Fedorov O, Heer J, Dixon DJ, Elkins JM, Knapp S, Bracher F, Brennan PE

Bioorg. Med. Chem.. doi: 10.1016/j.bmc.2018.03.020

Publication date: March 12, 2018

PMID: 29567296

Discovery of Small-Molecule Antagonists of the H3K9me3 Binding to UHRF1 Tandem Tudor Domain.

Senisterra G, Zhu HY, Luo X, Zhang H, Xun G, Lu C, Xiao W, Hajian T, Loppnau P, Chau I, Li F, Allali-Hassani A, Atadja P, Oyang C, Li E, Brown PJ, Arrowsmith CH, Zhao K, Yu Z, Vedadi M

SLAS Discov. 2472555218766278. doi: 10.1177/2472555218766278

Publication date: March 1, 2018

PMID: 29562800

Structural and histone binding studies of the chromo barrel domain of TIP60.

Zhang Y, Lei M, Yang X, Feng Y, Yang Y, Loppnau P, Li Y, Yang Y, Min J, Liu Y

FEBS Lett.. doi: 10.1002/1873-3468.13021

Publication date: March 1, 2018

PMID: 29494751

Creation of a novel class of potent and selective MutT Homolog 1 (MTH1) inhibitors using fragment-based screening and structure-based drug design.

Rahm F, Viklund J, Tresaugues L, Ellermann M, Giese A, Ericsson U, Forsblom R, Ginman T, Günther J, Hallberg K, Lindström J, Persson LB, Silvander C, Talagas A, Díaz-Sáez L, Fedorov O, Huber KVM, Panagakou I, Siejka P, Gorjanacz M, Bauser M, Andersson M

J. Med. Chem.. doi: 10.1021/acs.jmedchem.7b01884

Publication date: February 27, 2018

PMID: 29485874

Oocyte DNA damage quality control requires consecutive interplay of CHK2 and CK1 to activate p63.

Tuppi M, Kehrloesser S, Coutandin DW, Rossi V, Luh LM, Strubel A, Hötte K, Hoffmeister M, Schäfer B, De Oliveira T, Greten F, Stelzer EHK, Knapp S, De Felici M, Behrends C, Klinger FG, Dötsch V

Nat. Struct. Mol. Biol.. doi: 10.1038/s41594-018-0035-7

Publication date: February 26, 2018

PMID: 29483652

Structure activity relationship studies on rhodanines and derived enethiol inhibitors of metallo-β-lactamases.

Zhang D, Markoulides MS, Stepanovs D, Rydzik AM, El-Hussein A, Bon C, Kamps JJAG, Umland KD, Collins PM, Cahill ST, Wang DY, von Delft F, Brem J, McDonough MA, Schofield CJ

Bioorg. Med. Chem.. doi: 10.1016/j.bmc.2018.02.043

Publication date: February 23, 2018

PMID: 29655609

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

Vu H, Pedro L, Mak T, McCormick B, Rowley J, Liu M, Di Capua A, Williams-Noonan B, Pham NB, Pouwer RH, Nguyen B, Andrews KT, Skinner-Adams T, Kim J, Hol WGJ, Hui R, Crowther GJ, Van Voorhis WC, Quinn RJ

ACS Infect Dis. doi: 10.1021/acsinfecdis.7b00197

Publication date: February 13, 2018

PMID: 29436819

Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation.

Zheng Y, Sethi R, Mangala LS, Taylor C, Goldsmith J, Wang M, Masuda K, Karaminejadranjbar M, Mannion D, Miranda F, Herrero-Gonzalez S, Hellner K, Chen F, Alsaadi A, Albukhari A, Fotso DC, Yau C, Jiang D, Pradeep S, Rodriguez-Aguayo C, Lopez-Berestein G, Knapp S, Gray NS, Campo L, Myers KA, Dhar S, Ferguson D, Bast RC, Sood AK, von Delft F, Ahmed AA

Nat Commun. 9(1):476. doi: 10.1038/s41467-017-02811-7

Publication date: February 2, 2018

PMID: 29396402

Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors.

Suebsuwong C, Pinkas DM, Ray SS, Bufton JC, Dai B, Bullock AN, Degterev A, Cuny GD

Bioorg. Med. Chem. Lett.. doi: 10.1016/j.bmcl.2018.01.044

Publication date: January 31, 2018

PMID: 29409752

An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells.

Schrade K, Tröger J, Eldahshan A, Zühlke K, Abdul Azeez KR, Elkins JM, Neuenschwander M, Oder A, Elkewedi M, Jaksch S, Andrae K, Li J, Fernandes J, Müller PM, Grunwald S, Marino SF, Vukićević T, Eichhorst J, Wiesner B, Weber M, Kapiloff M, Rocks O, Daumke O, Wieland T, Knapp S, von Kries JP, Klussmann E

PLoS ONE. 13(1):e0191423. doi: 10.1371/journal.pone.0191423

Publication date: January 27, 2018

PMID: 29373579

CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function.

Canning P, Park K, Gonçalves J, Li C, Howard CJ, Sharpe TD, Holt LJ, Pelletier L, Bullock AN, Leroux MR

Cell Rep. 22(4):885-894. doi: 10.1016/j.celrep.2017.12.083

Publication date: January 23, 2018

PMID: 29420175

Cloning, expression and purification of kinase domains of cacao PR-1 receptor-like kinases.

Tosarini TR, Ramos PZ, de Souza GP, Baroni RM, Massirer KB, Couñago RM, Mondego JMC

Protein Expr. Purif.. doi: 10.1016/j.pep.2018.01.004

Publication date: January 19, 2018

PMID: 29360581

Discovery of Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT).

Babault N, Allali-Hassani A, Li F, Fan J, Yue A, Ju K, Liu F, Vedadi M, Liu J, Jin J

J. Med. Chem.. doi: 10.1021/acs.jmedchem.7b01422

Publication date: January 10, 2018

PMID: 29320176

Revealing the Protein Propionylation Activity of the Histone Acetyltransferase Males absent on the first (MOF).

Han Z, Wu H, Kim S, Yang X, Li Q, Huang H, Cai H, Bartlett MG, Dong A, Zeng H, Brown PJ, Yang X, Arrowsmith CH, Zhao Y, Zheng YG

J. Biol. Chem.. doi: 10.1074/jbc.RA117.000529

Publication date: January 10, 2018

PMID: 29321206

---Inhibition of histone H3K27 demethylase selectively modulates inflammatory phenotypes of natural killer cells.

Cribbs A, Hookway ES, Wells G, Lindow M, Obad S, Oerum H, Prinjha RK, Athanasou N, Sowman A, Philpott M, Penn H, Soderstrom K, Feldmann M, Oppermann U

J. Biol. Chem.. doi: 10.1074/jbc.RA117.000698

Publication date: January 4, 2018

PMID: 29301935

DNA Sequence Recognition of Human CXXC Domains and Their Structural Determinants.

Xu C, Liu K, Lei M, Yang A, Li Y, Hughes TR, Min J

Structure. doi: 10.1016/j.str.2017.11.022

Publication date: December 16, 2017

PMID: 29276034

Discovery of Potent and Selective Allosteric Inhibitors of Protein Arginine Methyltransferase 3 (PRMT3).

Kaniskan HÜ, Eram MS, Zhao K, Szewczyk MM, Yang X, Schmidt K, Luo X, Xiao S, Dai M, He F, Zang I, Lin Y, Li F, Dobrovetsky E, Smil D, Min SJ, Lin-Jones J, Schapira M, Atadja P, Li E, Barsyte-Lovejoy D, Arrowsmith CH, Brown PJ, Liu F, Yu Z, Vedadi M, Jin J

J. Med. Chem.. doi: 10.1021/acs.jmedchem.7b01674

Publication date: December 15, 2017

PMID: 29244490

H3K14ac is linked to methylation of H3K9 by the triple Tudor domain of SETDB1.

Jurkowska RZ, Qin S, Kungulovski G, Tempel W, Liu Y, Bashtrykov P, Stiefelmaier J, Jurkowski TP, Kudithipudi S, Weirich S, Tamas R, Wu H, Dombrovski L, Loppnau P, Reinhardt R, Min J, Jeltsch A

Nat Commun. 8(1):2057. doi: 10.1038/s41467-017-02259-9

Publication date: December 12, 2017

PMID: 29234025

The BEACH-domain containing protein, Nbeal2, interacts with Dock7, Sec16a and Vac14.

Mayer L, Jasztal M, Pardo M, Aguera de Haro S, Collins J, Bariana TK, Smethurst PA, Grassi L, Petersen R, Nurden P, Favier R, Yu L, Meacham S, Astle WJ, Choudhary J, Yue WW, Ouwehand WH, Guerrero JA

Blood. doi: 10.1182/blood-2017-08-800359

Publication date: November 29, 2017

PMID: 29187380

Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival.

Segatto M, Fittipaldi R, Pin F, Sartori R, Dae Ko K, Zare H, Fenizia C, Zanchettin G, Pierobon ES, Hatakeyama S, Sperti C, Merigliano S, Sandri M, Filippakopoulos P, Costelli P, Sartorelli V, Caretti G

Nat Commun. 8(1):1707. doi: 10.1038/s41467-017-01645-7

Publication date: November 22, 2017

PMID: 29167426

Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers.

Zuliani-Alvarez L, Marzeda AM, Deligne C, Schwenzer A, McCann FE, Marsden BD, Piccinini AM, Midwood KS

Nat Commun. 8(1):1595. doi: 10.1038/s41467-017-01718-7

Publication date: November 17, 2017

PMID: 29150600

Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors.

Dahlin JL, Nelson KM, Strasser JM, Barsyte-Lovejoy D, Szewczyk MM, Organ S, Cuellar M, Singh G, Shrimp JH, Nguyen N, Meier JL, Arrowsmith CH, Brown PJ, Baell JB, Walters MA

Nat Commun. 8(1):1527. doi: 10.1038/s41467-017-01657-3

Publication date: November 15, 2017

PMID: 29142305

Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement.

Vasta JD, Corona CR, Wilkinson J, Zimprich CA, Hartnett JR, Ingold MR, Zimmerman K, Machleidt T, Kirkland TA, Huwiler KG, Ohana RF, Slater M, Otto P, Cong M, Wells CI, Berger BT, Hanke T, Glas C, Ding K, Drewry DH, Huber KVM, Willson TM, Knapp S, Müller S, Meisenheimer PL, Fan F, Wood KV, Robers MB

Cell Chem Biol. doi: 10.1016/j.chembiol.2017.10.010

Publication date: November 13, 2017

PMID: 29174542

Structural basis for arginine methylation-independent recognition of PIWIL1 by TDRD2.

Zhang H, Liu K, Izumi N, Huang H, Ding D, Ni Z, Sidhu SS, Chen C, Tomari Y, Min J

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1711486114

Publication date: November 8, 2017

PMID: 29118143

The SGC beyond structural genomics: redefining the role of 3D structures by coupling genomic stratification with fragment-based discovery.

Bradley AR, Echalier A, Fairhead M, Strain-Damerell C, Brennan P, Bullock AN, Burgess-Brown NA, Carpenter EP, Gileadi O, Marsden BD, Lee WH, Yue W, Bountra C, von Delft F

Essays Biochem.. 61(5):495-503. doi: 10.1042/EBC20170051

Publication date: November 8, 2017

PMID: 29118096

Exploiting a water network to achieve enthalpy-driven, bromodomain-selective BET inhibitors.

Shadrick WR, Slavish PJ, Chai SC, Waddell B, Connelly M, Low JA, Tallant C, Young BM, Bharatham N, Knapp S, Boyd VA, Morfouace M, Roussel MF, Chen T, Lee RE, Kiplin Guy R, Shelat AA, Potter PM

Bioorg. Med. Chem.. doi: 10.1016/j.bmc.2017.10.042

Publication date: November 4, 2017

PMID: 29170024

Conformational dynamics of the TTD-PHD histone reader module of UHRF1 reveals multiple histone binding states, allosteric regulation and druggability.

Houliston RS, Lemak A, Iqbal A, Ivanochko D, Duan S, Kaustov L, Ong MS, Fan L, Senisterra G, Brown PJ, Wang YX, Arrowsmith CH

J. Biol. Chem.. doi: 10.1074/jbc.M117.799700

Publication date: October 26, 2017

PMID: 29074623

Identification and Optimization of 4-Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase.

Asquith CRM, Laitinen T, Bennett JM, Godoi PH, East MP, Tizzard GJ, Graves LM, Johnson GL, Dornsife RE, Wells CI, Elkins JM, Willson TM, Zuercher W

ChemMedChem. doi: 10.1002/cmdc.201700663

Publication date: October 26, 2017

PMID: 29072804

Characterization of three druggable hotspots in the Aurora-A/TPX2 interaction using biochemical, biophysical and fragment-based approaches.

McIntyre PJ, Collins PM, Vrzal L, Birchall K, Arnold LH, Mpamhanga C, Coombs PJ, Burgess SG, Richards MW, Winter A, Veverka V, von Delft F, Merritt A, Bayliss R

ACS Chem. Biol.. doi: 10.1021/acschembio.7b00537

Publication date: October 18, 2017

PMID: 29045126

Isoform-selective ATAD2 chemical probe with novel chemical structure and unusual mode of action.

Fernández-Montalván AE, Berger M, Kuropka B, Koo SJ, Badock V, Weiske J, Puetter V, Holton SJ, Stöckigt D, Ter Laak A, Centrella PA, Clark MA, Dumelin CE, Sigel EA, Soutter HH, Troast DM, Zhang Y, Cuozzo JW, Keefe AD, Roche D, Rodeschini V, Chaikuad A, Díaz-Sáez L, Bennett JM, Fedorov O, Huber KVM, Huebner J, Weinmann H, Hartung IV, Gorjanacz M

ACS Chem. Biol.. doi: 10.1021/acschembio.7b00708

Publication date: October 18, 2017

PMID: 29043777

WD40 repeat domain proteins: a novel target class?

Schapira M, Tyers M, Torrent M, Arrowsmith CH

Nat Rev Drug Discov. doi: 10.1038/nrd.2017.179

Publication date: October 13, 2017

PMID: 29026209

Small molecule antagonists of the interaction between the histone deacetylase 6 zinc-finger domain and ubiquitin.

Harding RJ, Ferreira de Freitas R, Collins PM, Franzoni I, Ravichandran M, Ouyang H, Juarez-Ornelas KA, Lautens M, Schapira M, von Delft F, Santhakumar V, Arrowsmith CH

J. Med. Chem.. doi: 10.1021/acs.jmedchem.7b00933

Publication date: October 11, 2017

PMID: 29019676