Publications | Structural Genomics Consortium

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

A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer.

Mello SS, Valente LJ, Raj N, Seoane JA, Flowers BM, McClendon J, Bieging-Rolett KT, Lee J, Ivanochko D, Kozak MM, Chang DT, Longacre TA, Koong AC, Arrowsmith CH, Kim SK, Vogel H, Wood LD, Hruban RH, Curtis C, Attardi LD

Cancer Cell. 32(4):460-473.e6. doi: 10.1016/j.ccell.2017.09.007

Publication date: October 9, 2017

PMID: 29017057

Discovery of a selective allosteric inhibitor targeting macrodomain 2 of poly-adenosine-diphosphate-ribose polymerases 14.

Schuller M, Riedel K, Gibbs-Seymour I, Uth K, Sieg C, Gehring AP, Ahel I, Bracher F, Kessler BM, Elkins JM, Knapp S

ACS Chem. Biol.. doi: 10.1021/acschembio.7b00445

Publication date: October 9, 2017

PMID: 28991428

Synthesis and Demonstration of the Biological Relevance of sp(3) -rich Scaffolds Distantly Related to Natural Product Frameworks.

Foley DJ, Craven PGE, Collins PM, Doveston RG, Aimon A, Talon R, Churcher I, von Delft F, Marsden SP, Nelson A

Chemistry. doi: 10.1002/chem.201704169

Publication date: October 6, 2017

PMID: 28983993

Synthesis of kinase inhibitors containing a pentafluorosulfanyl moiety.

Sansook S, Ocasio CA, Day IJ, Tizzard GJ, Coles SJ, Fedorov O, Bennett JM, Elkins JM, Spencer J

Org. Biomol. Chem.. doi: 10.1039/c7ob02289a

Publication date: October 6, 2017

PMID: 28984325

Discovery of a highly selective cell-active inhibitor of KDM2/7.

Gerken P, Wolstenhulme J, Tumber A, Hatch S, Zhang Y, Müller S, Chandler S, Mair B, Li F, Nijman S, Konietzny R, Szommer T, Yapp C, Fedorov O, Benesch J, Vedadi M, Kessler B, Kawamura A, Brennan P, Smith MD

Angew. Chem. Int. Ed. Engl.. doi: 10.1002/anie.201706788

Publication date: October 4, 2017

PMID: 28976073

A systematic analysis of atomic protein-ligand interactions in the PDB.

Ferreira de Freitas R, Schapira M

Medchemcomm. 8(10):1970-1981. doi: 10.1039/c7md00381a

Publication date: October 1, 2017

PMID: 29308120

Correction for Bagarova et al., "Constitutively Active ALK2 Receptor Mutants Require Type II Receptor Cooperation".

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

Mol. Cell. Biol.. 37(19):. doi: 10.1128/MCB.00284-17

Publication date: October 1, 2017

PMID: 28899999

Disease Association and Druggability of WD40 Repeat Proteins.

Song R, Wang ZD, Schapira M

J. Proteome Res.. doi: 10.1021/acs.jproteome.7b00451

Publication date: September 28, 2017

PMID: 28956604

Structural Complexity in the KCTD Family of Cullin3-Dependent E3 Ubiquitin Ligases.

Pinkas DM, Sanvitale CE, Bufton JC, Sorrell FJ, Solcan N, Chalk R, Doutch J, Bullock AN

Biochem. J.. doi: 10.1042/BCJ20170527

Publication date: September 28, 2017

PMID: 28963344

Corrigendum: Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer.

Wang BD, Ceniccola K, Hwang S, Andrawis R, Horvath A, Freedman JA, Olender J, Knapp S, Ching T, Garmire L, Patel V, Garcia-Blanco MA, Patierno SR, Lee NH

Nat Commun. 8:16161. doi: 10.1038/ncomms16161

Publication date: September 27, 2017

PMID: 28952599

Crystal structure of the WD40 domain of human PRPF19.

Zhang Y, Li Y, Liang X, Zhu Z, Sun H, He H, Min J, Liao S, Liu Y

Biochem. Biophys. Res. Commun.. doi: 10.1016/j.bbrc.2017.09.145

Publication date: September 26, 2017

PMID: 28962858

Inhibition of calcium dependent protein kinase 1 (CDPK1) by pyrazolopyrimidine analogs decreases establishment and reoccurrence of central nervous system disease by Toxoplasma gondii.

Rutaganira FU, Barks J, Dhason MS, Wang Q, Lopez MS, Long S, Radke JB, Jones NG, Maddirala AR, Janetka JW, El Bakkouri M, Hui R, Shokat KM, Sibley LD

J. Med. Chem.. doi: 10.1021/acs.jmedchem.7b01192

Publication date: September 21, 2017

PMID: 28933846

Asymmetric mechanosensitivity in a eukaryotic ion channel.

Clausen MV, Jarerattanachat V, Carpenter EP, Sansom MSP, Tucker SJ

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1708990114

Publication date: September 18, 2017

PMID: 28923939

Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2.

Williams E, Bullock AN

Bone. doi: 10.1016/j.bone.2017.09.004

Publication date: September 12, 2017

PMID: 28918311

Increased 15-PGDH expression leads to dysregulated resolution responses in stromal cells from patients with chronic tendinopathy.

Dakin SG, Ly L, Colas RA, Oppermann U, Wheway K, Watkins B, Dalli J, Carr AJ

Sci Rep. 7(1):11009. doi: 10.1038/s41598-017-11188-y

Publication date: September 8, 2017

PMID: 28887458

ASCL1 Reorganizes Chromatin to Direct Neuronal Fate and Suppress Tumorigenicity of Glioblastoma Stem Cells.

Park NI, Guilhamon P, Desai K, McAdam RF, Langille E, O'Connor M, Lan X, Whetstone H, Coutinho FJ, Vanner RJ, Ling E, Prinos P, Lee L, Selvadurai H, Atwal G, Kushida M, Clarke ID, Voisin V, Cusimano MD, Bernstein M, Das S, Bader G, Arrowsmith CH, Angers S, Huang X, Lupien M, Dirks PB

Cell Stem Cell. 21(3):411. doi: 10.1016/j.stem.2017.08.008

Publication date: September 7, 2017

PMID: 28886368

RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes.

Reijnders MRF, Ansor NM, Kousi M, Yue WW, Tan PL, Clarkson K, Clayton-Smith J, Corning K, Jones JR, Lam WWK, Mancini GMS, Marcelis C, Mohammed S, Pfundt R, Roifman M, Cohn R, Chitayat D, Millard TH, Katsanis N, Brunner HG, Banka S

Am. J. Hum. Genet.. 101(3):466-477. doi: 10.1016/j.ajhg.2017.08.007

Publication date: September 7, 2017

PMID: 28886345

Novel patient missense mutations in the HSD17B10 gene affect dehydrogenase and mitochondrial tRNA modification functions of the encoded protein.

Oerum S, Roovers M, Leichsenring M, Acquaviva-Bourdain C, Beermann F, Gemperle-Britschgi C, Fouilhoux A, Korwitz-Reichelt A, Bailey HJ, Droogmans L, Oppermann U, Sass JO, Yue WW

Biochim. Biophys. Acta. doi: 10.1016/j.bbadis.2017.09.002

Publication date: September 6, 2017

PMID: 28888424

A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission.

Baker DA, Stewart LB, Large JM, Bowyer PW, Ansell KH, Jiménez-Díaz MB, El Bakkouri M, Birchall K, Dechering KJ, Bouloc NS, Coombs PJ, Whalley D, Harding DJ, Smiljanic-Hurley E, Wheldon MC, Walker EM, Dessens JT, Lafuente MJ, Sanz LM, Gamo FJ, Ferrer SB, Hui R, Bousema T, Angulo-Barturén I, Merritt AT, Croft SL, Gutteridge WE, Kettleborough CA, Osborne SA

Nat Commun. 8(1):430. doi: 10.1038/s41467-017-00572-x

Publication date: September 5, 2017

PMID: 28874661

First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor.

Moody JD, Levy S, Mathieu J, Xing Y, Kim W, Dong C, Tempel W, Robitaille AM, Dang LT, Ferreccio A, Detraux D, Sidhu S, Zhu L, Carter L, Xu C, Valensisi C, Wang Y, Hawkins RD, Min J, Moon RT, Orkin SH, Baker D, Ruohola-Baker H

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1706907114

Publication date: September 1, 2017

PMID: 28864533

Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy.

Lan X, Jörg DJ, Cavalli FMG, Richards LM, Nguyen LV, Vanner RJ, Guilhamon P, Lee L, Kushida MM, Pellacani D, Park NI, Coutinho FJ, Whetstone H, Selvadurai HJ, Che C, Luu B, Carles A, Moksa M, Rastegar N, Head R, Dolma S, Prinos P, Cusimano MD, Das S, Bernstein M, Arrowsmith CH, Mungall AJ, Moore RA, Ma Y, Gallo M, Lupien M, Pugh TJ, Taylor MD, Hirst M, Eaves CJ, Simons BD, Dirks PB

Nature. doi: 10.1038/nature23666

Publication date: August 30, 2017

PMID: 28854171

Role of remodeling and spacing factor 1 in histone H2A ubiquitination-mediated gene silencing.

Zhang Z, Jones AE, Wu W, Kim J, Kang Y, Bi X, Gu Y, Popov IK, Renfrow MB, Vassylyeva MN, Vassylyev DG, Giles KE, Chen D, Kumar A, Fan Y, Tong Y, Liu CF, An W, Chang C, Luo J, Chow LT, Wang H

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1711158114

Publication date: August 30, 2017

PMID: 28855339

Selective targeting of Bromodomains of the Bromodomain-PHD Fingers family impairs osteoclast differentiation.

Meier JC, Tallant C, Fedorov O, Witwicka H, Hwang SY, van Stiphout RG, Lambert JP, Rogers C, Yapp C, Gerstenberger BS, Fedele V, Savitsky P, Heidenreich D, Daniels DL, Owen DR, Fish PV, Igoe NM, Bayle ED, Haendler B, Oppermann UCT, Buffa F, Brennan PE, Müller S, Gingras AC, Odgren PR, Birnbaum MJ, Knapp S

ACS Chem. Biol.. doi: 10.1021/acschembio.7b00481

Publication date: August 29, 2017

PMID: 28849908

TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER-Golgi intermediate compartments.

Hanna MG, Block S, Frankel EB, Hou F, Johnson A, Yuan L, Knight G, Moresco JJ, Yates JR, Ashton R, Schekman R, Tong Y, Audhya A

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1709120114

Publication date: August 29, 2017

PMID: 28851831

Comprehensive Analysis of the Human SH3 Domain Family Reveals a Wide Variety of Non-canonical Specificities.

Teyra J, Huang H, Jain S, Guan X, Dong A, Liu Y, Tempel W, Min J, Tong Y, Kim PM, Bader GD, Sidhu SS

Structure. doi: 10.1016/j.str.2017.07.017

Publication date: August 28, 2017

PMID: 28890361

Tudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor protein.

Carr SM, Munro S, Sagum CA, Fedorov O, Bedford MT, La Thangue NB

Cell Death Differ.. doi: 10.1038/cdd.2017.135

Publication date: August 25, 2017

PMID: 28841214

A novel image-based high throughput screening assay discovers therapeutic candidates for adult polyglucosan body disease.

Solemsky LJ, Khazanov N, Senderowitz H, Wang P, Minassian BA, Ferreira IM, Yue WW, Lossos A, Weil M, Kakhlon O

Biochem. J.. doi: 10.1042/BCJ20170469

Publication date: August 21, 2017

PMID: 28827282

Studies on the Interaction of the Histone Demethylase KDM5B with Tricarboxylic Acid Cycle Intermediates.

Tarhonskaya H, Nowak RP, Johansson C, Szykowska A, Tumber A, Hancock RL, Lang P, Flashman E, Oppermann U, Schofield CJ, Kawamura A

J. Mol. Biol.. doi: 10.1016/j.jmb.2017.08.007

Publication date: August 18, 2017

PMID: 28827149

Characterization of a highly selective inhibitor of the Aurora kinases.

Ferguson FM, Doctor ZM, Chaikuad A, Sim T, Kim ND, Knapp S, Gray NS

Bioorg. Med. Chem. Lett.. doi: 10.1016/j.bmcl.2017.08.016

Publication date: August 10, 2017

PMID: 28818446

A statistical analysis on the performance of MMPBSA versus absolute binding free energy calculations: bromodomains as a case study.

Aldeghi M, Bodkin MJ, Knapp S, Biggin PC

J Chem Inf Model. doi: 10.1021/acs.jcim.7b00347

Publication date: August 8, 2017

PMID: 28786670

Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations.

Couñago RM, Allerston CK, Savitsky P, Azevedo H, Godoi PH, Wells CI, Mascarello A, de Souza Gama FH, Massirer KB, Zuercher WJ, Guimarães CRW, Gileadi O

Sci Rep. 7(1):7501. doi: 10.1038/s41598-017-07755-y

Publication date: August 8, 2017

PMID: 28790404