Publications | Structural Genomics Consortium

CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses.

Hammitzsch A, Tallant C, Fedorov O, O'Mahony A, Brennan PE, Hay DA, Martinez FO, Al-Mossawi MH, de Wit J, Vecellio M, Wells C, Wordsworth P, Müller S, Knapp S, Bowness P

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1501956112

Publication date: August 10, 2015

PMID: 26261308

Defined PEG smears as an alternative approach to enhance the search for crystallization conditions and crystal-quality improvement in reduced screens.

Chaikuad A, Knapp S, von Delft F

Acta Crystallogr. D Biol. Crystallogr.. 71(Pt 8):1627-39. doi: 10.1107/S1399004715007968

Publication date: August 1, 2015

PMID: 26249344

Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome.

Wu H, Zeng H, Lam R, Tempel W, Kerr ID, Min J

Acta Crystallogr F Struct Biol Commun. 71(Pt 8):981-5. doi: 10.1107/S2053230X15010183

Publication date: August 1, 2015

PMID: 26249686

A Call for Systematic Research on Solute Carriers.

César-Razquin A, Snijder B, Frappier-Brinton T, Isserlin R, Gyimesi G, Bai X, Reithmeier RA, Hepworth D, Hediger MA, Edwards AM, Superti-Furga G

Cell. 162(3):478-87. doi: 10.1016/j.cell.2015.07.022

Publication date: July 30, 2015

PMID: 26232220

BET inhibition upregulates SIRT1 and alleviates inflammatory responses.

Suuronen T, Pesonen M, Filippakopoulos P, Salminen A, Jarho EM, Lahtela-Kakkonen M, Kokkola T

Chembiochem. doi: 10.1002/cbic.201500272

Publication date: July 25, 2015

PMID: 26212199

Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase: implications for autoimmunity in rheumatoid arthritis.

Montgomery AB, Kopec J, Shrestha L, Thezenas ML, Burgess-Brown NA, Fischer R, Yue WW, Venables PJ

Ann. Rheum. Dis.. doi: 10.1136/annrheumdis-2015-207656

Publication date: July 24, 2015

PMID: 26209657

Discovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of Aldehyde Dehydrogenase 1A1 (ALDH1A1).

Yang SM, Yasgar A, Miller B, Lal-Nag M, Brimacombe K, Hu X, Sun H, Wang A, Xu X, Nguyen K, Oppermann U, Ferrer M, Vasiliou V, Simeonov A, Jadhav A, Maloney DJ

J. Med. Chem.. doi: 10.1021/acs.jmedchem.5b00577

Publication date: July 24, 2015

PMID: 26207746

A core of kinase-regulated interactomes defines the neoplastic MDSC lineage.

Gato-Cañas M, Martinez de Morentin X, Blanco-Luquin I, Fernandez-Irigoyen J, Zudaire I, Liechtenstein T, Arasanz H, Lozano T, Casares N, Chaikuad A, Knapp S, Guerrero-Setas D, Escors D, Kochan G, Santamaría E

Oncotarget.

Publication date: July 23, 2015

PMID: 26320174

Probing the epigenome.

Huston A, Arrowsmith CH, Knapp S, Schapira M

Nat. Chem. Biol.. 11(8):542-5. doi: 10.1038/nchembio.1871

Publication date: July 21, 2015

PMID: 26196765

Structural basis of glycogen branching enzyme deficiency and pharmacologic rescue by rational peptide design.

Froese DS, Michaeli A, McCorvie TJ, Krojer T, Sasi M, Melaev E, Goldblum A, Zatsepin M, Lossos A, Álvarez R, Escribá PV, Minaissan BA, von Delft F, Kakhlon O, Yue WW

Hum. Mol. Genet.. doi: 10.1093/hmg/ddv280

Publication date: July 21, 2015

PMID: 26199317

The promise and peril of chemical probes.

Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O'Hagan RC, Overington JP, Owen DR, Rosenberg SH, Roth B, Ross R, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, Zuercher WJ

Nat. Chem. Biol.. 11(8):536-41. doi: 10.1038/nchembio.1867

Publication date: July 21, 2015

PMID: 26196764

Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia.

Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Skucha A, Vittori S, Kuznetsova E, Smil D, Barsyte-Lovejoy D, Li F, Poda G, Schapira M, Wu H, Dong A, Senisterra G, Stukalov A, Huber KV, Schönegger A, Marcellus R, Bilban M, Bock C, Brown PJ, Zuber J, Bennett KL, Al-Awar R, Delwel R, Nerlov C, Arrowsmith CH, Superti-Furga G

Nat. Chem. Biol.. doi: 10.1038/nchembio.1859

Publication date: July 13, 2015

PMID: 26167872

Type II inhibitors targeting CDK2.

Alexander LT, Moebitz H, Drueckes P, Savitsky P, Fedorov O, Elkins JM, Deane CM, Cowan-Jacob SW, Knapp S

ACS Chem. Biol.. doi: 10.1021/acschembio.5b00398

Publication date: July 9, 2015

PMID: 26158339

Designing selective inhibitors for calcium-dependent protein kinases in apicomplexans.

Hui R, El Bakkouri M, Sibley LD

Trends Pharmacol. Sci.. doi: 10.1016/j.tips.2015.04.011

Publication date: July 5, 2015

PMID: 26002073

Beating the odds: BETs in disease.

Wang CY, Filippakopoulos P

Trends Biochem. Sci.. doi: 10.1016/j.tibs.2015.06.002

Publication date: July 2, 2015

PMID: 26145250

Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies.

Belaya K, Rodríguez Cruz PM, Liu WW, Maxwell S, McGowan S, Farrugia ME, Petty R, Walls TJ, Sedghi M, Basiri K, Yue WW, Sarkozy A, Bertoli M, Pitt M, Kennett R, Schaefer A, Bushby K, Parton M, Lochmüller H, Palace J, Muntoni F, Beeson D

Brain. doi: 10.1093/brain/awv185

Publication date: June 30, 2015

PMID: 26133662

Assessment of a method to characterize antibody selectivity and specificity for use in immunoprecipitation.

Marcon E, Jain H, Bhattacharya A, Guo H, Phanse S, Pu S, Byram G, Collins BC, Dowdell E, Fenner M, Guo X, Hutchinson A, Kennedy JJ, Krastins B, Larsen B, Lin ZY, Lopez MF, Loppnau P, Miersch S, Nguyen T, Olsen JB, Paduch M, Ravichandran M, Seitova A, Vadali G, Vogelsang MS, Whiteaker JR, Zhong G, Zhong N, Zhao L, Aebersold R, Arrowsmith CH, Emili A, Frappier L, Gingras AC, Gstaiger M, Paulovich AG, Koide S, Kossiakoff AA, Sidhu SS, Wodak SJ, Gräslund S, Greenblatt JF, Edwards AM

Nat. Methods. doi: 10.1038/nmeth.3472

Publication date: June 29, 2015

PMID: 26121405

Structural Basis for the Specificity of Human NUDT16 and Its Regulation by Inosine Monophosphate.

Trésaugues L, Lundbäck T, Welin M, Flodin S, Nyman T, Silvander C, Gräslund S, Nordlund P

PLoS ONE. 10(6):e0131507. doi: 10.1371/journal.pone.0131507

Publication date: June 29, 2015

PMID: 26121039

Mechanisms underlying clinical efficacy of Angiotensin II type 2 receptor (AT2R) antagonist EMA401 in neuropathic pain: clinical tissue and in vitro studies.

Anand U, Yiangou Y, Sinisi M, Fox M, MacQuillan A, Quick T, Korchev YE, Bountra C, McCarthy T, Anand P

Mol Pain. 11(1):38. doi: 10.1186/s12990-015-0038-x

Publication date: June 26, 2015

PMID: 26111701

Biochemical characterization of FIKK8-a unique protein kinase from the malaria parasite Plasmodium falciparum and other apicomplexans.

Osman K, Lou HJ, Qiu W, Brand V, Edwards AM, Turk BE, Hui R

Mol. Biochem. Parasitol.. doi: 10.1016/j.molbiopara.2015.06.002

Publication date: June 22, 2015

PMID: 26112892

Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2.

Sweis RF, Wang Z, Algire M, Arrowsmith CH, Brown PJ, Chiang GG, Guo J, Jakob CG, Kennedy S, Li F, Maag D, Shaw B, Soni NB, Vedadi M, Pappano WN

ACS Med Chem Lett. 6(6):695-700. doi: 10.1021/acsmedchemlett.5b00124

Publication date: June 11, 2015

PMID: 26101576

Tankyrase 1 Inhibitors with Drug-like Properties Identified by Screening a DNA-Encoded Chemical Library.

Samain F, Ekblad T, Mikutis G, Zhong N, Zimmermann M, Nauer A, Bajic D, Decurtins W, Scheuermann J, Brown PJ, Hall J, Gräslund S, Schüler H, Neri D, Franzini RM

J. Med. Chem.. doi: 10.1021/acs.jmedchem.5b00432

Publication date: June 10, 2015

PMID: 26061013

Pim Kinase Inhibitors Evaluated with a Single-Molecule Engineered Nanopore Sensor.

Harrington L, Alexander LT, Knapp S, Bayley H

Angew. Chem. Int. Ed. Engl.. doi: 10.1002/anie.201503141

Publication date: June 8, 2015

PMID: 26058458

Structural Basis of KEAP1 Interactions with Nrf2.

Canning P, Sorrell FJ, Bullock AN

Free Radic. Biol. Med.. doi: 10.1016/j.freeradbiomed.2015.05.034

Publication date: June 6, 2015

PMID: 26057936

MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes.

Stansfeld PJ, Goose JE, Caffrey M, Carpenter EP, Parker JL, Newstead S, Sansom MS

Structure. doi: 10.1016/j.str.2015.05.006

Publication date: May 28, 2015

PMID: 26073602

Kinetic characterization of human histone H3 lysine 36 methyltransferases, ASH1L and SETD2.

Eram MS, Kuznetsova E, Li F, Lima-Fernandes E, Kennedy S, Chau I, Arrowsmith CH, Schapira M, Vedadi M

Biochim. Biophys. Acta. doi: 10.1016/j.bbagen.2015.05.013

Publication date: May 19, 2015

PMID: 26002201

LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor.

Clark PG, Vieira LC, Tallant C, Fedorov O, Singleton DC, Rogers CM, Monteiro OP, Bennett JM, Baronio R, Müller S, Daniels DL, Méndez J, Knapp S, Brennan PE, Dixon DJ

Angew Chem Weinheim Bergstr Ger. 127(21):6315-6319. doi: 10.1002/ange.201501394

Publication date: May 18, 2015

PMID: 27346896

Discovery of a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and BRPF.

Bennett JM, Fedorov O, Tallant C, Monteiro OP, Meier J, Gamble V, Savitski P, Nunez-Alonso GA, Haendler B, Rogers C, Brennan PE, Müller S, Knapp S

J. Med. Chem.. doi: 10.1021/acs.jmedchem.5b00458

Publication date: May 14, 2015

PMID: 25974391

Structural diversity of the epigenetics pocketome.

Cabaye A, Nguyen KT, Liu L, Pande V, Schapira M

Proteins. doi: 10.1002/prot.24830

Publication date: May 13, 2015

PMID: 25974248

Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes.

Newman JA, Savitsky P, Allerston CK, Bizard AH, Özer Ö, Sarlós K, Liu Y, Pardon E, Steyaert J, Hickson ID, Gileadi O

Nucleic Acids Res.. doi: 10.1093/nar/gkv373

Publication date: April 21, 2015

PMID: 25901030

Solution-state NMR structure of the putative morphogene protein BolA (PFE0790c) from Plasmodium falciparum.

Buchko GW, Yee A, Semesi A, Myler PJ, Arrowsmith CH, Hui R

Acta Crystallogr F Struct Biol Commun. 71(Pt 5):514-21. doi: 10.1107/S2053230X1402799X

Publication date: April 18, 2015

PMID: 25945703

LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor.

Clark PG, Vieira LC, Tallant C, Fedorov O, Singleton DC, Rogers CM, Monteiro OP, Bennett JM, Baronio R, Müller S, Daniels DL, Méndez J, Knapp S, Brennan PE, Dixon DJ

Angew. Chem. Int. Ed. Engl.. doi: 10.1002/anie.201501394

Publication date: April 13, 2015

PMID: 25864491

Structures of the Ets Domains of Transcription Factors ETV1, ETV4, ETV5 and FEV: Determinants of DNA Binding and Redox Regulation by Disulfide bond formation.

Cooper CD, Newman JA, Aitkenhead H, Allerston CK, Gileadi O

J. Biol. Chem.. doi: 10.1074/jbc.M115.646737

Publication date: April 12, 2015

PMID: 25866208

Discovery of a Dual PRMT5-PRMT7 Inhibitor.

Smil D, Eram MS, Li F, Kennedy S, Szewczyk MM, Brown PJ, Barsyte-Lovejoy D, Arrowsmith CH, Vedadi M, Schapira M

ACS Med Chem Lett. 6(4):408-12. doi: 10.1021/ml500467h

Publication date: April 9, 2015

PMID: 25893041

Perspective on Computational and Structural Aspects of Kinase Discovery from IPK2014.

Martin E, Knapp S, Engh RA, Moebitz H, Varin T, Roux B, Meiler J, Berdini V, Baumann A, Vieth M

Biochim. Biophys. Acta. doi: 10.1016/j.bbapap.2015.03.014

Publication date: April 7, 2015

PMID: 25861861

Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation.

Liu K, Liu Y, Lau JL, Min J

Pharmacol. Ther.. doi: 10.1016/j.pharmthera.2015.04.001

Publication date: April 6, 2015

PMID: 25857453

Structural and evolutionary divergence of cyclic nucleotide binding domains in eukaryotic pathogens: Implications for drug design.

Mohanty S, Kennedy EJ, Herberg FW, Hui R, Taylor SS, Langsley G, Kannan N

Biochim. Biophys. Acta. doi: 10.1016/j.bbapap.2015.03.012

Publication date: April 3, 2015

PMID: 25847873

LLY-507, a Cell-Active, Potent and Selective Inhibitor of Protein Lysine Methyltransferase SMYD2.

Nguyen H, Allali-Hassani A, Antonysamy S, Chang S, Chen LH, Curtis C, Emtage S, Fan L, Gheyi T, Li F, Liu S, Martin JR, Mendel D, Olsen JB, Pelletier L, Shatseva T, Wu S, Zhang FF, Arrowsmith CH, Brown PJ, Campbell RM, Garcia BA, Barsyte-Lovejoy D, Mader M, Vedadi M

J. Biol. Chem.. doi: 10.1074/jbc.M114.626861

Publication date: March 30, 2015

PMID: 25825497

Selective inhibitors of Cyclin-G associated kinase (GAK) as anti-HCV agents.

Kovackova S, Chang L, Bekerman E, Neveu G, Barouch-Bentov R, Chaikuad A, Heroven C, Sala M, De Jonghe SC, Knapp S, Einav S, Herdewijn P

J. Med. Chem.. doi: 10.1021/jm501759m

Publication date: March 30, 2015

PMID: 25822739

Discovery and characterization of GSK2801, a selective chemical probe for the bromodomains BAZ2A and BAZ2B.

Chen P, Chaikuad A, Bamborough P, Bantscheff M, Bountra C, Chung CW, Fedorov O, Grandi P, Jung D, Lesniak R, Lindon M, Müller S, Philpott M, Prinjha RK, Rogers CM, Selenski C, Tallant C, Werner T, Willson TM, Knapp S, Drewry DH

J. Med. Chem.. doi: 10.1021/acs.jmedchem.5b00209

Publication date: March 23, 2015

PMID: 25799074

Human RECQ1 helicase-driven DNA unwinding, annealing, and branch migration: Insights from DNA complex structures.

Pike AC, Gomathinayagam S, Swuec P, Berti M, Zhang Y, Schnecke C, Marino F, von Delft F, Renault L, Costa A, Gileadi O, Vindigni A

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1417594112

Publication date: March 23, 2015

PMID: 25831490

K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.

Dong YY, Pike AC, Mackenzie A, McClenaghan C, Aryal P, Dong L, Quigley A, Grieben M, Goubin S, Mukhopadhyay S, Ruda GF, Clausen MV, Cao L, Brennan PE, Burgess-Brown NA, Sansom MS, Tucker SJ, Carpenter EP

Science. 347(6227):1256-1259. doi: 10.1126/science.1261512

Publication date: March 13, 2015

PMID: 25766236

10-Iodo-11H-indolo[3,2-c]quinoline-6-carboxylic Acids Are Selective Inhibitors of DYRK1A.

Falke H, Chaikuad A, Becker A, Loaëc N, Lozach O, Abu Jhaisha S, Becker W, Jones PG, Preu L, Baumann K, Knapp S, Meijer L, Kunick C

J. Med. Chem.. doi: 10.1021/jm501994d

Publication date: March 2, 2015

PMID: 25730262

A Potent, Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 3 (PRMT3).

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

Angew. Chem. Int. Ed. Engl.. doi: 10.1002/anie.201412154

Publication date: February 27, 2015

PMID: 25728001

Ankyrin Repeats of ANKRA2 Recognize a PxLPxL Motif on the 3M Syndrome Protein CCDC8.

Nie J, Xu C, Jin J, Aka JA, Tempel W, Nguyen V, You L, Weist R, Min J, Pawson T, Yang XJ

Structure. doi: 10.1016/j.str.2015.02.001

Publication date: February 26, 2015

PMID: 25752541

Structure Enabled Design of BAZ2-ICR, A Chemical Probe Targeting the Bromodomains of BAZ2A and BAZ2B.

Drouin L, McGrath S, Vidler LR, Chaikuad A, Monteiro O, Tallant C, Philpott M, Rogers C, Fedorov O, Liu M, Akhtar W, Hayes A, Raynaud F, Müller S, Knapp S, Hoelder S

J. Med. Chem.. doi: 10.1021/jm501963e

Publication date: February 26, 2015

PMID: 25719566

Building a roadmap for developing combination therapies for Alzheimer's disease.

Perry D, Sperling R, Katz R, Berry D, Dilts D, Hanna D, Salloway S, Trojanowski JQ, Bountra C, Krams M, Luthman J, Potkin S, Gribkoff V, Temple R, Wang Y, Carrillo MC, Stephenson D, Snyder H, Liu E, Ware T, McKew J, Fields FO, Bain LJ, Bens C

Expert Rev Neurother. 15(3):327-33. doi: 10.1586/14737175.2015.996551

Publication date: February 25, 2015

PMID: 25708309

The 9H-purine scaffold reveals induced-fit pocket plasticity of the BRD9 bromodomain.

Picaud S, Strocchia M, Terracciano S, Lauro G, Méndez J, Daniels DL, Riccio R, Bifulco G, Bruno I, Filippakopoulos P

J. Med. Chem.. doi: 10.1021/jm501893k

Publication date: February 22, 2015

PMID: 25703523

Preclinical target validation using patient-derived cells.

Edwards AM, Arrowsmith CH, Bountra C, Bunnage ME, Feldmann M, Knight JC, Patel DD, Prinos P, Taylor MD, Sundström M, Barker P, Barsyte D, Bengtson MH, Bell C, Bowness P, Boycott KM, Buser-Doepner C, Carpenter CL, Carr AJ, Clark K, Das AM, Dhanak D, Dirks P, Ellis J, Fantin VR, Flores C, Fon EA, Frail DE, Gileadi O, O'Hagan RC, Howe T, Isaac JT, Jabado N, Jakobsson PJ, Klareskog L, Knapp S, Lee WH, Lima-Fernandes E, Lundberg IE, Marshall J, Massirer KB, MacKenzie AE, Maruyama T, Mueller-Fahrnow A, Muthuswamy S, Nanchahal J, O'Brien C, Oppermann U, Ostermann N, Petrecca K, Pollock BG, Poupon V, Prinjha RK, Rosenberg SH, Rouleau G, Skingle M, Slutsky AS, Smith GA, Verhelle D, Widmer H, Young LT

Nat Rev Drug Discov. 14(3):149-50. doi: 10.1038/nrd4565

Publication date: February 20, 2015

PMID: 25722227

Structural Insights into the Auto-regulation and Cooperativity of the Human Transcription Factor Ets-2.

Newman JA, Cooper CD, Aitkenhead H, Gileadi O

J. Biol. Chem.. doi: 10.1074/jbc.M114.619270

Publication date: February 10, 2015

PMID: 25670864