Publications | Structural Genomics Consortium

Targeting Pim Kinases and DAPK3 to Control Hypertension.

Carlson DA, Singer MR, Sutherland C, Redondo C, Alexander LT, Hughes PF, Knapp S, Gurley SB, Sparks MA, MacDonald JA, Haystead TAJ

Cell Chem Biol. doi: 10.1016/j.chembiol.2018.06.006

Publication date: July 4, 2018

PMID: 30033129

Identification of Rpl29 as a major substrate of the lysine methyltransferase Set7/9.

Hamidi T, Singh AK, Veland N, Vemulapalli V, Chen J, Hardikar S, Bao J, Fry CJ, Yang V, Lee KA, Guo A, Arrowsmith CH, Bedford MT, Chen T

J. Biol. Chem.. doi: 10.1074/jbc.RA118.002890

Publication date: June 29, 2018

PMID: 29959229

A Bench-Stable Transfer Reagent for the Synthesis of Trifluoromethyl-sulfonimidamides from Sulfinamides.

Wright M, Martinez-Lamenca C, Leenaerts JE, Brennan PE, Trabanco AA, Oehlrich D

J. Org. Chem.. doi: 10.1021/acs.joc.8b01244

Publication date: June 22, 2018

PMID: 29932332

New tools for carbohydrate sulphation analysis: Heparan Sulphate 2- O -sulphotransferase (HS2ST) is a target for small molecule protein kinase inhibitors.

Byrne DP, Li Y, Ramakrishnan K, Barsukov IL, Yates EA, Eyers CE, Papy-Garcia D, Chantepie S, Pagadala V, Lu J, Wells C, Drewry DH, Zuercher WJ, Berry NG, Fernig DG, Eyers PA

Biochem. J.. doi: 10.1042/BCJ20180265

Publication date: June 22, 2018

PMID: 29934491

New tools for evaluating protein tyrosine sulphation: Tyrosyl Protein Sulphotransferases (TPSTs) are novel targets for RAF protein kinase inhibitors.

Byrne DP, Li Y, Ngamlert P, Ramakrishnan K, Eyers CE, Wells C, Drewry DH, Zuercher WJ, Berry NG, Fernig DG, Eyers PA

Biochem. J.. doi: 10.1042/BCJ20180266

Publication date: June 22, 2018

PMID: 29934490

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

Casey AE, Sinha A, Singhania R, Livingstone J, Waterhouse P, Tharmapalan P, Cruickshank J, Shehata M, Drysdale E, Fang H, Kim H, Isserlin R, Bailey S, Medina T, Deblois G, Shiah YJ, Barsyte-Lovejoy D, Hofer S, Bader G, Lupien M, Arrowsmith C, Knapp S, De Carvalho D, Berman H, Boutros PC, Kislinger T, Khokha R

J. Cell Biol.. doi: 10.1083/jcb.201804042

Publication date: June 19, 2018

PMID: 29921600

Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition.

Froese DS, Kopec J, Rembeza E, Bezerra GA, Oberholzer AE, Suormala T, Lutz S, Chalk R, Borkowska O, Baumgartner MR, Yue WW

Nat Commun. 9(1):2261. doi: 10.1038/s41467-018-04735-2

Publication date: June 11, 2018

PMID: 29891918

Structural insight into the human mitochondrial tRNA purine N1-methyltransferase and Ribonuclease P complexes.

Oerum S, Roovers M, Rambo RP, Kopec J, Bailey HJ, Fitzpatrick F, Newman JA, Newman WG, Amberger A, Zschocke J, Droogmans L, Oppermann U, Yue WW

J. Biol. Chem.. doi: 10.1074/jbc.RA117.001286

Publication date: June 7, 2018

PMID: 29880640

A DNA-Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition.

Favalli N, Biendl S, Hartmann M, Piazzi J, Sladojevich F, Gräslund S, Brown PJ, Näreoja K, Schüler H, Scheuermann J, Franzini R, Neri D

ChemMedChem. doi: 10.1002/cmdc.201800193

Publication date: June 1, 2018

PMID: 29856130

Development, Optimization and Structure-Activity Relationships of Covalent-Reversible JAK3 Inhibitors Based on a Tricyclic Imidazo[5,4-d]pyrrolo[2,3-b]pyridine Scaffold.

Forster M, Chaikuad A, Dimitrov T, Döring E, Holstein J, Berger BT, Gehringer M, Ghoreschi K, Müller S, Knapp S, Laufer SA

J. Med. Chem.. doi: 10.1021/acs.jmedchem.8b00571

Publication date: May 31, 2018

PMID: 29852068

What Is the BET on Solid Tumors?

Filippakopoulos P

J. Clin. Oncol.. JCO2018788695. doi: 10.1200/JCO.2018.78.8695

Publication date: May 30, 2018

PMID: 29847297

ZMPSTE24 missense mutations that cause progeroid diseases decrease prelamin A cleavage activity and/or protein stability.

Spear ED, Hsu ET, Nie L, Carpenter EP, Hrycyna CA, Michaelis S

Dis Model Mech. doi: 10.1242/dmm.033670

Publication date: May 24, 2018

PMID: 29794150

The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms.

Fulcher LJ, Bozatzi P, Tachie-Menson T, Wu KZL, Cummins TD, Bufton JC, Pinkas DM, Dunbar K, Shrestha S, Wood NT, Weidlich S, Macartney TJ, Varghese J, Gourlay R, Campbell DG, Dingwell KS, Smith JC, Bullock AN, Sapkota GP

Sci Signal. 11(531):. doi: 10.1126/scisignal.aao2341

Publication date: May 22, 2018

PMID: 29789297

1,2,6-Thiadiazinones as Novel Narrow Spectrum Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) Inhibitors.

Asquith CRM, Godoi PH, Couñago RM, Laitinen T, Scott JW, Langendorf CG, Oakhill JS, Drewry DH, Zuercher WJ, Koutentis PA, Willson TM, Kalogirou AS

Molecules. 23(5):. doi: 10.3390/molecules23051221

Publication date: May 19, 2018

PMID: 29783765

BET bromodomain ligands: Probing the WPF shelf to improve BRD4 bromodomain affinity and metabolic stability.

Jennings LE, Schiedel M, Hewings DS, Picaud S, Laurin CMC, Bruno PA, Bluck JP, Scorah AR, See L, Reynolds JK, Moroglu M, Mistry IN, Hicks A, Guzanov P, Clayton J, Evans CNG, Stazi G, Biggin PC, Mapp AK, Hammond EM, Humphreys PG, Filippakopoulos P, Conway SJ

Bioorg. Med. Chem.. doi: 10.1016/j.bmc.2018.05.003

Publication date: May 15, 2018

PMID: 29776834

DOT1L inhibition attenuates graft-versus-host disease by allogeneic T cells in adoptive immunotherapy models.

Kagoya Y, Nakatsugawa M, Saso K, Guo T, Anczurowski M, Wang CH, Butler MO, Arrowsmith CH, Hirano N

Nat Commun. 9(1):1915. doi: 10.1038/s41467-018-04262-0

Publication date: May 15, 2018

PMID: 29765028

Identification and Structure-Activity Relationship of HDAC6 Zinc-Finger Ubiquitin Binding Domain Inhibitors.

Ferreira de Freitas R, Harding RJ, Franzoni I, Ravichandran M, Mann MK, Ouyang H, Lautens M, Santhakumar V, Arrowsmith CH, Schapira M

J. Med. Chem.. doi: 10.1021/acs.jmedchem.8b00258

Publication date: May 9, 2018

PMID: 29741882

Molecular structures of cdc2-like kinases in complex with a new inhibitor chemotype.

Walter A, Chaikuad A, Helmer R, Loaëc N, Preu L, Ott I, Knapp S, Meijer L, Kunick C

PLoS ONE. 13(5):e0196761. doi: 10.1371/journal.pone.0196761

Publication date: May 4, 2018

PMID: 29723265

Application of Integrated Drug Screening/Kinome Analysis to Identify Inhibitors of Gemcitabine-Resistant Pancreatic Cancer Cell Growth.

Krulikas LJ, McDonald IM, Lee B, Okumu DO, East MP, Gilbert TSK, Herring LE, Golitz BT, Wells CI, Axtman AD, Zuercher WJ, Willson TM, Kireev D, Yeh JJ, Johnson GL, Baines AT, Graves LM

SLAS Discov. 2472555218773045. doi: 10.1177/2472555218773045

Publication date: May 1, 2018

PMID: 29742358

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