Publications | Structural Genomics Consortium

X-ray Crystal Structure of ERK5 (MAPK7) in Complex with a Specific Inhibitor.

Elkins JM, Wang J, Deng X, Pattison MJ, Arthur JS, Erazo T, Gomez N, Lizcano JM, Gray NS, Knapp S

J. Med. Chem.. doi: 10.1021/jm4000837

Publication date: May 17, 2013

Restoring p53 Function in Human Melanoma Cells by Inhibiting MDM2 and Cyclin B1/CDK1-Phosphorylated Nuclear iASPP.

Lu M, Breyssens H, Salter V, Zhong S, Hu Y, Baer C, Ratnayaka I, Sullivan A, Brown NR, Endicott J, Knapp S, Kessler BM, Middleton MR, Siebold C, Jones EY, Sviderskaya EV, Cebon J, John T, Caballero OL, Goding CR, Lu X

Cancer Cell. 23(5):618-33. doi: 10.1016/j.ccr.2013.03.013

Publication date: May 13, 2013

PMID: 23623661

A New Class of Small Molecule Inhibitor of BMP Signaling.

Sanvitale CE, Kerr G, Chaikuad A, Ramel MC, Mohedas AH, Reichert S, Wang Y, Triffitt JT, Cuny GD, Yu PB, Hill CS, Bullock AN

PLoS ONE. 8(4):e62721. doi: 10.1371/journal.pone.0062721

Publication date: April 30, 2013

PMID: 23646137

Development of an ALK2-Biased BMP Type I Receptor Kinase Inhibitor.

Mohedas AH, Xing X, Armstrong KA, Bullock AN, Cuny GD, Yu PB

ACS Chem. Biol.. doi: 10.1021/cb300655w

Publication date: April 30, 2013

PMID: 23547776

An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1.

Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, Macnevin CJ, Liu F, Gao C, Huang XP, Kuznetsova E, Rougie M, Jiang A, Pattenden SG, Norris JL, James LI, Roth BL, Brown PJ, Frye SV, Arrowsmith CH, Hahn KM, Wang GG, Vedadi M, Jin J

ACS Chem. Biol.. doi: 10.1021/cb400133j

Publication date: April 24, 2013

PMID: 23614352

Selective Bisubstrate Inhibitors with Sub-nanomolar Affinity for Protein Kinase Pim-1.

Ekambaram R, Enkvist E, Vaasa A, Kasari M, Raidaru G, Knapp S, Uri A

ChemMedChem. 8(6):909-13. doi: 10.1002/cmdc.201300042

Publication date: April 24, 2013

PMID: 23616352

Constitutively Active ALK2 Receptor Mutants Require Type II Receptor Cooperation.

Bagarova J, Vonner AJ, Armstrong KA, Börgermann J, Lai CS, Deng DY, Beppu H, Alfano I, Filippakopoulos P, Morrell NW, Bullock AN, Knaus P, Mishina Y, Yu PB

Mol. Cell. Biol.. 33(12):2413-24. doi: 10.1128/MCB.01595-12

Publication date: April 9, 2013

PMID: 23572558

Construction of human activity-based phosphorylation networks.

Newman RH, Hu J, Rho HS, Xie Z, Woodard C, Neiswinger J, Cooper C, Shirley M, Clark HM, Hu S, Hwang W, Jeong JS, Wu G, Lin J, Gao X, Ni Q, Goel R, Xia S, Ji H, Dalby KN, Birnbaum MJ, Cole PA, Knapp S, Ryazanov AG, Zack DJ, Blackshaw S, Pawson T, Gingras AC, Desiderio S, Pandey A, Turk BE, Zhang J, Zhu H, Qian J

Mol. Syst. Biol.. 9:655. doi: 10.1038/msb.2013.12

Publication date: April 4, 2013

PMID: 23549483

Why is epigenetics important in understanding the pathogenesis of inflammatory musculoskeletal diseases?

Oppermann U

Arthritis Res. Ther.. 15(2):209. doi: 10.1186/ar4186

Publication date: April 3, 2013

PMID: 23566317

Bromo-deaza-SAH: A potent and selective DOT1L inhibitor.

Yu W, Smil D, Li F, Tempel W, Fedorov O, Nguyen KT, Bolshan Y, Al-Awar R, Knapp S, Arrowsmith CH, Vedadi M, Brown PJ, Schapira M

Bioorg. Med. Chem.. 21(7):1787-94. doi: 10.1016/j.bmc.2013.01.049

Publication date: April 1, 2013

PMID: 23433670

Crystal structures of Klebsiella pneumoniae pantothenate kinase in complex with N-substituted pantothenamides.

Li B, Tempel W, Smil D, Bolshan Y, Schapira M, Park HW

Proteins. doi: 10.1002/prot.24290

Publication date: March 30, 2013

PMID: 23553820

The structural basis of ZMPSTE24-dependent laminopathies.

Quigley A, Dong YY, Pike AC, Dong L, Shrestha L, Berridge G, Stansfeld PJ, Sansom MS, Edwards AM, Bountra C, von Delft F, Bullock AN, Burgess-Brown NA, Carpenter EP

Science. 339(6127):1604-7. doi: 10.1126/science.1231513

Publication date: March 29, 2013

PMID: 23539603

Inhibition of BET Bromodomain Targets Genetically Diverse Glioblastoma.

Cheng Z, Gong Y, Ma Y, Lu K, Lu X, Pierce LA, Thompson RC, Muller S, Knapp S, Wang J

Clin. Cancer Res.. doi: 10.1158/1078-0432.CCR-12-3066

Publication date: March 26, 2013

PMID: 23403638

Optimization of 3,5-dimethylisoxazole derivatives as potent BET bromodomain ligands.

Hewings DS, Fedorov O, Filippakopoulos P, Martin S, Picaud S, Tumber A, Wells C, Olcina MM, Freeman K, Gill A, Ritchie AJ, Sheppard DW, Russell AJ, Hammond EM, Knapp S, Brennan PE, Conway SJ

J. Med. Chem.. doi: 10.1021/jm301588r

Publication date: March 21, 2013

PMID: 23517011

Structural Basis for Cul3 Protein Assembly with the BTB-Kelch Family of E3 Ubiquitin Ligases.

Canning P, Cooper CD, Krojer T, Murray JW, Pike AC, Chaikuad A, Keates T, Thangaratnarajah C, Hojzan V, Marsden BD, Gileadi O, Knapp S, von Delft F, Bullock AN

J. Biol. Chem.. 288(11):7803-14. doi: 10.1074/jbc.M112.437996

Publication date: March 15, 2013

PMID: 23349464

Exploiting an Allosteric Binding Site of PRMT3 Yields Potent and Selective Inhibitors.

Liu F, Li F, Ma A, Dobrovetsky E, Dong A, Gao C, Korboukh I, Liu J, Smil D, Brown PJ, Frye SV, Arrowsmith CH, Schapira M, Vedadi M, Jin J

J. Med. Chem.. 56(5):2110-24. doi: 10.1021/jm3018332

Publication date: March 14, 2013

PMID: 23445220

Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists of WDR5-MLL Interaction.

Bolshan Y, Getlik M, Kuznetsova E, Wasney GA, Hajian T, Poda G, Nguyen KT, Wu H, Dombrovski L, Dong A, Senisterra G, Schapira M, Arrowsmith CH, Brown PJ, Al-Awar R, Vedadi M, Smil D

ACS Med Chem Lett. 4(3):353-7. doi: 10.1021/ml300467n

Publication date: March 14, 2013

PMID: 24900672

Systems approaches to genomic and epigenetic inter-regulation of peptide hormones in stress and reproduction.

Lovejoy DA, Barsyte-Lovejoy D

Prog. Biophys. Mol. Biol.. doi: 10.1016/j.pbiomolbio.2013.02.002

Publication date: March 14, 2013

PMID: 23500148

Crystal structures of the catalytic domain of human soluble guanylate cyclase.

Allerston CK, von Delft F, Gileadi O

PLoS ONE. 8(3):e57644. doi: 10.1371/journal.pone.0057644

Publication date: March 7, 2013

PMID: 23505436

Strategy to Target the Substrate Binding site of SET Domain Protein Methyltransferases.

Nguyen KT, Li F, Poda G, Smil D, Vedadi M, Schapira M

J Chem Inf Model. doi: 10.1021/ci300596x

Publication date: March 1, 2013

PMID: 23410263

Insight into S-adenosyl-L-methionine biosynthesis from crystal structures of human methionine adenosyltransferase catalytic and regulatory subunits.

Shafqat N, Muniz JR, Pilka ES, Paragrigoriou E, von Delft F, Oppermann U, Yue WW

Biochem. J.. doi: 10.1042/BJ20121580

Publication date: February 20, 2013

PMID: 23425511

A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency.

Shafqat N, Kavanagh KL, Sass JO, Christensen E, Fukao T, Lee WH, Oppermann U, Yue WW

J. Inherit. Metab. Dis.. doi: 10.1007/s10545-013-9589-z

Publication date: February 19, 2013

PMID: 23420214

A small molecule inhibitor of the BLM helicase modulates chromosome stability in human cells.

Nguyen GH, Dexheimer TS, Rosenthal AS, Chu WK, Singh DK, Mosedale G, Bachrati CZ, Schultz L, Sakurai M, Savitsky P, Abu M, McHugh PJ, Bohr VA, Harris CC, Jadhav A, Gileadi O, Maloney DJ, Simeonov A, Hickson ID

Chem. Biol.. 20(1):55-62. doi: 10.1016/j.chembiol.2012.10.016

Publication date: January 24, 2013

PMID: 23352139

Solution structure of the Big domain from Streptococcus pneumoniae reveals a novel Ca2+-binding module.

Wang T, Zhang J, Zhang X, Xu C, Tu X

Sci Rep. 3:1079. doi: 10.1038/srep01079

Publication date: January 16, 2013

PMID: 23326635

Novel Inverse Binding Mode of Indirubin Derivatives Yields Improved Selectivity for DYRK Kinases.

Myrianthopoulos V, Kritsanida M, Gaboriaud-Kolar N, Magiatis P, Ferandin Y, Durieu E, Lozach O, Cappel D, Soundararajan M, Filippakopoulos P, Sherman W, Knapp S, Meijer L, Mikros E, Skaltsounis AL

ACS Med Chem Lett. 4(1):22-26. doi: 10.1021/ml300207a

Publication date: January 10, 2013

PMID: 23336033

LRIG2 Mutations Cause Urofacial Syndrome.

Stuart HM, Roberts NA, Burgu B, Daly SB, Urquhart JE, Bhaskar S, Dickerson JE, Mermerkaya M, Silay MS, Lewis MA, Olondriz MB, Gener B, Beetz C, Varga RE, Gülpınar O, Süer E, Soygür T, Ozçakar ZB, Yalçınkaya F, Kavaz A, Bulum B, Gücük A, Yue WW, Erdogan F, Berry A, Hanley NA, McKenzie EA, Hilton EN, Woolf AS, Newman WG

Am. J. Hum. Genet.. doi: 10.1016/j.ajhg.2012.12.002

Publication date: January 9, 2013

PMID: 23313374

Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain.

James LI, Barsyte-Lovejoy D, Zhong N, Krichevsky L, Korboukh VK, Herold JM, Macnevin CJ, Norris JL, Sagum CA, Tempel W, Marcon E, Guo H, Gao C, Huang XP, Duan S, Emili A, Greenblatt JF, Kireev DB, Jin J, Janzen WP, Brown PJ, Bedford MT, Arrowsmith CH, Frye SV

Nat. Chem. Biol.. doi: 10.1038/nchembio.1157

Publication date: January 6, 2013

PMID: 23292653

Structural Insights into the Activation of MST3 by MO25.

Mehellou Y, Alessi DR, Macartney TJ, Szklarz M, Knapp S, Elkins JM

Biochem. Biophys. Res. Commun.. doi: 10.1016/j.bbrc.2012.12.113

Publication date: January 4, 2013

PMID: 23296203

A Strategy for Modulation of Enzymes in the Ubiquitin System.

Ernst A, Avvakumov G, Tong J, Fan Y, Zhao Y, Alberts P, Persaud A, Walker JR, Neculai AM, Neculai D, Vorobyov A, Garg P, Beatty L, Chan PK, Juang YC, Landry MC, Yeh C, Zeqiraj E, Karamboulas K, Allali-Hassani A, Vedadi M, Tyers M, Moffat J, Sicheri F, Pelletier L, Durocher D, Raught B, Rotin D, Yang J, Moran MF, Dhe-Paganon S, Sidhu SS

Science. doi: 10.1126/science.1230161

Publication date: January 3, 2013

PMID: 23287719

Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5.

Senisterra G, Wu H, Allali-Hassani A, Wasney GA, Barsyte-Lovejoy D, Dombrovski L, Dong A, Nguyen KT, Smil D, Bolshan Y, Hajian T, He H, Seitova A, Chau I, Li F, Poda G, Couture JF, Brown PJ, Al-Awar R, Schapira M, Arrowsmith CH, Vedadi M

Biochem. J.. 449(1):151-9. doi: 10.1042/BJ20121280

Publication date: January 1, 2013

PMID: 22989411

The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains.

Hay D, Fedorov O, Filippakopoulos P, Martin S, Philpott M, Picaud S, Hewings DS, Uttakar S, Heightman TD, Conway SJ, Knapp S, Brennan PE

Medchemcomm. 4(1):140-144. doi: 10.1039/C2MD20189E

Publication date: January 1, 2013

PMID: 26682033

(R)-β-lysine modified elongation factor P functions in translation elongation.

Bullwinkle TJ, Zou SB, Rajkovic A, Hersch SJ, Elgamal S, Robinson N, Smil D, Bolshan Y, Navarre WW, Ibba M

J. Biol. Chem.. doi: 10.1074/jbc.M112.438879

Publication date: December 31, 2012

PMID: 23277358

Crystal Structure of the Human SUV39H1 Chromodomain and Its Recognition of Histone H3K9me2/3.

Wang T, Xu C, Liu Y, Fan K, Li Z, Sun X, Ouyang H, Zhang X, Zhang J, Li Y, Mackenzie F, Min J, Tu X

PLoS ONE. 7(12):e52977. doi: 10.1371/journal.pone.0052977

Publication date: December 28, 2012

PMID: 23285239

Nahuoic Acid A Produced by a Streptomyces sp. Isolated From a Marine Sediment Is a Selective SAM-Competitive Inhibitor of the Histone Methyltransferase SETD8.

Williams DE, Dalisay DS, Li F, Amphlett J, Maneerat W, Chavez MA, Wang YA, Matainaho T, Yu W, Brown PJ, Arrowsmith CH, Vedadi M, Andersen RJ

Org. Lett.. doi: 10.1021/ol303416k

Publication date: December 28, 2012

PMID: 23272941

Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors.

Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E, Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ, Arrowsmith CH, Bradner JE, Schapira M

Nat Commun. 3:1288. doi: 10.1038/ncomms2304

Publication date: December 18, 2012

PMID: 23250418

A public-private partnership to unlock the untargeted kinome.

Knapp S, Arruda P, Blagg J, Burley S, Drewry DH, Edwards A, Fabbro D, Gillespie P, Gray NS, Kuster B, Lackey KE, Mazzafera P, Tomkinson NC, Willson TM, Workman P, Zuercher WJ

Nat. Chem. Biol.. 9(1):3-6. doi: 10.1038/nchembio.1113

Publication date: December 15, 2012

PMID: 23238671

Bromodomain-containing Protein 4 (BRD4) Regulates RNA Polymerase II Serine 2 Phosphorylation in Human CD4+ T Cells.

Zhang W, Prakash C, Sum C, Gong Y, Li Y, Kwok JJ, Thiessen N, Pettersson S, Jones SJ, Knapp S, Yang H, Chin KC

J. Biol. Chem.. 287(51):43137-55. doi: 10.1074/jbc.M112.413047

Publication date: December 14, 2012

PMID: 23086925

Tet3 CXXC Domain and Dioxygenase Activity Cooperatively Regulate Key Genes for Xenopus Eye and Neural Development.

Xu Y, Xu C, Kato A, Tempel W, Abreu JG, Bian C, Hu Y, Hu D, Zhao B, Cerovina T, Diao J, Wu F, He HH, Cui Q, Clark E, Ma C, Barbara A, Veenstra GJ, Xu G, Kaiser UB, Liu XS, Sugrue SP, He X, Min J, Kato Y, Shi YG

Cell. 151(6):1200-13. doi: 10.1016/j.cell.2012.11.014

Publication date: December 7, 2012

PMID: 23217707

Tudor domains of the PRC2 components PHF1 and PHF19 selectively bind to histone H3K36me3.

Qin S, Guo Y, Xu C, Bian C, Fu M, Gong S, Min J

Biochem. Biophys. Res. Commun.. doi: 10.1016/j.bbrc.2012.11.116

Publication date: December 7, 2012

PMID: 23228662

CDR-H3 Diversity Is Not Required for Antigen Recognition by Synthetic Antibodies.

Persson H, Ye W, Wernimont A, Adams JJ, Koide A, Koide S, Lam R, Sidhu SS

J. Mol. Biol.. doi: 10.1016/j.jmb.2012.11.037

Publication date: December 3, 2012

PMID: 23219464

Certhrax Toxin, an Anthrax-related ADP-ribosyltransferase from Bacillus cereus.

Visschedyk D, Rochon A, Tempel W, Dimov S, Park HW, Merrill AR

J. Biol. Chem.. 287(49):41089-102. doi: 10.1074/jbc.M112.412809

Publication date: November 30, 2012

PMID: 22992735

Epigallocatechin-3-gallate up-regulates tumor suppressor gene expression via a reactive oxygen species-dependent down-regulation of UHRF1.

Achour M, Mousli M, Alhosin M, Ibrahim A, Peluso J, Muller CD, Schini-Kerth VB, Hamiche A, Dhe-Paganon S, Bronner C

Biochem. Biophys. Res. Commun.. doi: 10.1016/j.bbrc.2012.11.087

Publication date: November 28, 2012

PMID: 23201574

Structural insights into the inactive subunit of the apicoplast-localized caseinolytic protease complex of Plasmodium falciparum.

El Bakkouri M, Rathore S, Calmettes C, Wernimont AK, Liu K, Sinha D, Asad M, Jung P, Hui R, Mohmmed A, Houry WA

J. Biol. Chem.. doi: 10.1074/jbc.M112.416560

Publication date: November 28, 2012

PMID: 23192353

Identification of a Chemical Probe for Bromo and Extra C-Terminal Bromodomain Inhibition through Optimization of a Fragment-Derived Hit.

Fish PV, Filippakopoulos P, Bish G, Brennan PE, Bunnage ME, Cook AS, Federov O, Gerstenberger BS, Jones H, Knapp S, Marsden B, Nocka K, Owen DR, Philpott M, Picaud S, Primiano MJ, Ralph MJ, Sciammetta N, Trzupek JD

J. Med. Chem.. 55(22):9831-7. doi: 10.1021/jm3010515

Publication date: November 26, 2012

PMID: 23095041

Progress in the Development and Application of Small Molecule Inhibitors of Bromodomain-Acetyl-lysine Interactions.

Hewings DS, Rooney TP, Jennings LE, Hay DA, Schofield CJ, Brennan PE, Knapp S, Conway SJ

J. Med. Chem.. 55(22):9393-413. doi: 10.1021/jm300915b

Publication date: November 26, 2012

PMID: 22924434

Histone recognition by human malignant brain tumor domains.

Nady N, Krichevsky L, Zhong N, Duan S, Tempel W, Amaya MF, Ravichandran M, Arrowsmith CH

J. Mol. Biol.. 423(5):702-18. doi: 10.1016/j.jmb.2012.08.022

Publication date: November 9, 2012

PMID: 22954662

Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B.

Tahtouh T, Elkins JM, Filippakopoulos P, Soundararajan M, Burgy G, Durieu E, Cochet C, Schmid RS, Lo DC, Delhommel F, Oberholzer AE, Pearl LH, Carreaux F, Bazureau JP, Knapp S, Meijer L

J. Med. Chem.. 55(21):9312-30. doi: 10.1021/jm301034u

Publication date: November 8, 2012

PMID: 22998443

Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization.

Twigg SR, Lloyd D, Jenkins D, Elçioglu NE, Cooper CD, Al-Sannaa N, Annagür A, Gillessen-Kaesbach G, Hüning I, Knight SJ, Goodship JA, Keavney BD, Beales PL, Gileadi O, McGowan SJ, Wilkie AO

Am. J. Hum. Genet.. 91(5):897-905. doi: 10.1016/j.ajhg.2012.08.027

Publication date: November 2, 2012

PMID: 23063620

Structural basis for ASPP2 recognition by the tumor suppressor p73.

Canning P, von Delft F, Bullock AN

J. Mol. Biol.. 423(4):515-27. doi: 10.1016/j.jmb.2012.08.005

Publication date: November 2, 2012

PMID: 22917970

Sinefungin derivatives as inhibitors and structure probes of protein lysine methyltransferase SETD2.

Zheng W, Ibáñez G, Wu H, Blum G, Zeng H, Dong A, Li F, Hajian T, Allali-Hassani A, Amaya MF, Siarheyeva A, Yu W, Brown PJ, Schapira M, Vedadi M, Min J, Luo M

J. Am. Chem. Soc.. 134(43):18004-14. doi: 10.1021/ja307060p

Publication date: October 31, 2012

PMID: 23043551