Publications | Structural Genomics Consortium

Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition.

Halabelian L, Ravichandran M, Li Y, Zeng H, Rao A, Aravind L, Arrowsmith CH

Nat. Struct. Mol. Biol.. doi: 10.1038/s41594-019-0246-6

Publication date: June 24, 2019

Insights into the full-length SRPK2 structure and its hydrodynamic behavior.

de Almeida Alves Barbosa É, Seraphim TV, Gandin CA, Teixeira LF, da Silva RAG, Righetto GL, Goncalves KA, de Souza Vasconcellos R, de Almeida Lamêgo MR, Júnior AS, Fietto JLR, Kobarg J, Gileadi C, Massirer KB, Borges JC, de Oliveira Neto M, Bressan GC

Int. J. Biol. Macromol.. doi: 10.1016/j.ijbiomac.2019.06.135

Publication date: June 20, 2019

PMID: 31229549

Structure-guided fragment-based drug discovery at the synchrotron: screening binding sites and correlations with hotspot mapping.

Thomas SE, Collins P, James RH, Mendes V, Charoensutthivarakul S, Radoux C, Abell C, Coyne AG, Floto RA, von Delft F, Blundell TL

Philos Trans A Math Phys Eng Sci. 377(2147):20180422. doi: 10.1098/rsta.2018.0422

Publication date: June 17, 2019

PMID: 31030650

Expanding the genetic and phenotypic spectrum of branched-chain amino acid transferase 2 deficiency.

Knerr I, Colombo R, Urquhart J, Morais A, Merinero B, Oyarzabal A, Pérez B, Jones SA, Perveen R, Preece MA, Rogers Y, Treacy EP, Mayne P, Zampino G, MacKinnon S, Wassmer E, Yue WW, Robinson I, Rodríguez-Pombo P, Olpin SE, Banka S

J. Inherit. Metab. Dis.. doi: 10.1002/jimd.12135

Publication date: June 8, 2019

PMID: 31177572

Structural and functional consequences of the STAT5BN642H driver mutation.

de Araujo ED, Erdogan F, Neubauer HA, Meneksedag-Erol D, Manaswiyoungkul P, Eram MS, Seo HS, Qadree AK, Israelian J, Orlova A, Suske T, Pham HTT, Boersma A, Tangermann S, Kenner L, Rülicke T, Dong A, Ravichandran M, Brown PJ, Audette GF, Rauscher S, Dhe-Paganon S, Moriggl R, Gunning PT

Nat Commun. 10(1):2517. doi: 10.1038/s41467-019-10422-7

Publication date: June 7, 2019

PMID: 31175292

15-deoxy-Δ12,14-Prostaglandin J2 inhibits human soluble epoxide hydrolase by a dual orthosteric and allosteric mechanism.

Abis G, Charles RL, Kopec J, Yue WW, Atkinson RA, Bui TTT, Lynham S, Popova S, Sun YB, Fraternali F, Eaton P, Conte MR

Commun Biol. 2:188. doi: 10.1038/s42003-019-0426-2

Publication date: May 28, 2019

PMID: 31123712

A Ubiquitin-Binding Domain that Binds a Structural Fold Distinct from that of Ubiquitin.

Lim M, Newman JA, Williams HL, Masino L, Aitkenhead H, Gravard AE, Gileadi O, Svejstrup JQ

Structure. doi: 10.1016/j.str.2019.05.003

Publication date: May 28, 2019

PMID: 31204252

Synthesis and structure-activity relationships of 3,5-disubstituted-pyrrolo[2,3- b]pyridines as inhibitors of adaptor associated kinase 1 (AAK1) with antiviral activity.

Verdonck S, Pu SY, Sorrell FJ, Elkins JM, Froeyen M, Gao LJ, Prugar LI, Dorosky DE, Brannan JM, Barouch-Bentov R, Knapp S, Dye JM, Herdewijn P, Einav S, De Jonghe S

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b00136

Publication date: May 28, 2019

PMID: 31136173

ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma.

Carvalho D, Taylor KR, Olaciregui NG, Molinari V, Clarke M, Mackay A, Ruddle R, Henley A, Valenti M, Hayes A, Brandon AH, Eccles SA, Raynaud F, Boudhar A, Monje M, Popov S, Moore AS, Mora J, Cruz O, Vinci M, Brennan PE, Bullock AN, Carcaboso AM, Jones C

Commun Biol. 2:156. doi: 10.1038/s42003-019-0420-8

Publication date: May 18, 2019

PMID: 31098401

Increased EZH2 expression in prostate cancer is associated with metastatic recurrence following external beam radiotherapy.

Wu X, Scott H, Carlsson SV, Sjoberg DD, Cerundolo L, Lilja H, Prevo R, Rieunier G, Macaulay V, Higgins GS, Verrill CL, Lamb AD, Cunliffe VT, Bountra C, Hamdy FC, Bryant RJ

Prostate. doi: 10.1002/pros.23817

Publication date: May 18, 2019

PMID: 31104332

Targeting protein methylation: from chemical tools to precision medicines.

Dilworth D, Barsyte-Lovejoy D

Cell. Mol. Life Sci.. doi: 10.1007/s00018-019-03147-9

Publication date: May 18, 2019

PMID: 31104094

15-deoxy-Δ12,14-Prostaglandin J2 inhibits human soluble epoxide hydrolase by a dual orthosteric and allosteric mechanism.

Abis G, Charles RL, Kopec J, Yue WW, Atkinson RA, Bui TTT, Lynham S, Popova S, Sun YB, Fraternali F, Eaton P, Conte MR

Commun Biol. 2(1):188. doi: 10.1038/s42003-019-0426-2

Publication date: May 17, 2019

PMID: 31925008

C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays.

Le Bihan YV, Lanigan RM, Atrash B, McLaughlin MG, Velupillai S, Malcolm AG, England KS, Ruda GF, Mok NY, Tumber A, Tomlin K, Saville H, Shehu E, McAndrew C, Carmichael L, Bennett JM, Jeganathan F, Eve P, Donovan A, Hayes A, Wood F, Raynaud FI, Fedorov O, Brennan PE, Burke R, van Montfort RLM, Rossanese OW, Blagg J, Bavetsias V

Eur J Med Chem. 177:316-337. doi: 10.1016/j.ejmech.2019.05.041

Publication date: May 17, 2019

PMID: 31158747

Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism.

Fox NG, Yu X, Feng X, Bailey HJ, Martelli A, Nabhan JF, Strain-Damerell C, Bulawa C, Yue WW, Han S

Nat Commun. 10(1):2210. doi: 10.1038/s41467-019-09989-y

Publication date: May 17, 2019

PMID: 31101807

Utilizing comprehensive and mini-kinome panels to optimize the selectivity of quinoline inhibitors for cyclin G associated kinase (GAK).

Asquith CRM, Treiber DK, Zuercher WJ

Bioorg. Med. Chem. Lett.. doi: 10.1016/j.bmcl.2019.05.025

Publication date: May 16, 2019

PMID: 31129055

The dynamic conformational landscape of the protein methyltransferase SETD8.

Chen S, Wiewiora RP, Meng F, Babault N, Ma A, Yu W, Qian K, Hu H, Zou H, Wang J, Fan S, Blum G, Pittella-Silva F, Beauchamp KA, Tempel W, Jiang H, Chen K, Skene RJ, Zheng YG, Brown PJ, Jin J, Luo C, Chodera JD, Luo M

Elife. 8:. doi: 10.7554/eLife.45403

Publication date: May 13, 2019

PMID: 31081496

ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma.

Carvalho D, Taylor KR, Olaciregui NG, Molinari V, Clarke M, Mackay A, Ruddle R, Henley A, Valenti M, Hayes A, Brandon AH, Eccles SA, Raynaud F, Boudhar A, Monje M, Popov S, Moore AS, Mora J, Cruz O, Vinci M, Brennan PE, Bullock AN, Carcaboso AM, Jones C

Commun Biol. 2(1):156. doi: 10.1038/s42003-019-0420-8

Publication date: May 9, 2019

PMID: 31925004

Rapid covalent-probe discovery by electrophile-fragment screening.

Resnick E, Bradley A, Gan J, Douangamath A, Krojer T, Sethi R, Geurink PP, Aimon A, Amitai G, Bellini D, Bennett J, Fairhead M, Fedorov O, Gabizon R, Gan J, Guo J, Plotnikov A, Reznik N, Ruda GF, Díaz-Sáez L, Straub VM, Szommer T, Velupillai S, Zaidman D, Zhang Y, Coker AR, Dowson CG, Barr H, Wang C, Huber KVM, Brennan PE, Ovaa H, von Delft F, London N

J. Am. Chem. Soc.. doi: 10.1021/jacs.9b02822

Publication date: May 7, 2019

PMID: 31060360

Structure and function of eTudor domain containing TDRD proteins.

Gan B, Chen S, Liu H, Min J, Liu K

Crit. Rev. Biochem. Mol. Biol.. 1-14. doi: 10.1080/10409238.2019.1603199

Publication date: May 3, 2019

PMID: 31046474

A Perspective on Extreme Open Science: Companies Sharing Compounds without Restriction.

Drewry DH, Wells CI, Zuercher WJ, Willson TM

SLAS Discov. 2472555219838210. doi: 10.1177/2472555219838210

Publication date: April 29, 2019

PMID: 31034310

Construction of a Shape-Diverse Fragment Set: Design, Synthesis and Screen against Aurora-A Kinase.

Zhang R, McIntyre PJ, Collins PM, Foley DJ, Arter C, von Delft F, Bayliss R, Warriner S, Nelson A

Chemistry. doi: 10.1002/chem.201900815

Publication date: April 26, 2019

PMID: 31026091

Crosstalk between RNA Pol II C-Terminal Domain Acetylation and Phosphorylation via RPRD Proteins.

Ali I, Ruiz DG, Ni Z, Johnson JR, Zhang H, Li PC, Khalid MM, Conrad RJ, Guo X, Min J, Greenblatt J, Jacobson M, Krogan NJ, Ott M

Mol. Cell. doi: 10.1016/j.molcel.2019.04.008

Publication date: April 26, 2019

PMID: 31054975

Crystal structure of human RIOK2 bound to a specific inhibitor.

Wang J, Varin T, Vieth M, Elkins JM

Open Biol. 9(4):190037. doi: 10.1098/rsob.190037

Publication date: April 26, 2019

PMID: 30991936

Discovery of selective activators of PRC2 mutant EED-I363M.

Suh JL, Barnash KD, Abramyan TM, Li F, The J, Engelberg IA, Vedadi M, Brown PJ, Kireev DB, Arrowsmith CH, James LI, Frye SV

Sci Rep. 9(1):6524. doi: 10.1038/s41598-019-43005-z

Publication date: April 25, 2019

PMID: 31024026

A chemical toolbox for the study of bromodomains and epigenetic signaling.

Wu Q, Heidenreich D, Zhou S, Ackloo S, Krämer A, Nakka K, Lima-Fernandes E, Deblois G, Duan S, Vellanki RN, Li F, Vedadi M, Dilworth J, Lupien M, Brennan PE, Arrowsmith CH, Müller S, Fedorov O, Filippakopoulos P, Knapp S

Nat Commun. 10(1):1915. doi: 10.1038/s41467-019-09672-2

Publication date: April 23, 2019

PMID: 31015424

Design of a Cyclin G Associated Kinase (GAK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Set to Interrogate the Relationship of EGFR and GAK in Chordoma.

Asquith CRM, Naegeli KM, East MP, Laitinen T, Havener TM, Wells CI, Johnson GL, Drewry DH, Zuercher WJ, Morris DC

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b00350

Publication date: April 19, 2019

PMID: 30973735

Discovery of Pyrrolo[3,2-d]pyrimidin-4-one Derivatives as a New Class of Potent and Cell Active Inhibitors of P300/CBP-Associated Factor Bromodomain.

Huang LY, Li H, Li LL, Niu L, Seupel R, Wu C, Cheng W, Chen C, Ding B, Brennan PE, Yang S

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b00096

Publication date: April 18, 2019

PMID: 30998845

Structural analyses reveal that MBD3 is a methylated-CG binder.

Liu K, Lei M, Wu Z, Gan B, Cheng H, Li Y, Min J

FEBS J.. doi: 10.1111/febs.14850

Publication date: April 13, 2019

PMID: 30980593

Structural insights into the modulatory role of the accessory protein WYL1 in the Type VI-D CRISPR-Cas system.

Zhang H, Dong C, Li L, Wasney GA, Min J

Nucleic Acids Res.. doi: 10.1093/nar/gkz269

Publication date: April 12, 2019

PMID: 30976796

Chromokinesins NOD and KID Use Distinct ATPase Mechanisms and Microtubule Interactions to Perform a Similar Function.

Walker BC, Tempel W, Zhu H, Park HW, Cochran JC

Biochemistry. doi: 10.1021/acs.biochem.9b00011

Publication date: April 11, 2019

PMID: 30973712

A Tail-Based Mechanism Drives Nucleosome Demethylation by the LSD2/NPAC Multimeric Complex.

Marabelli C, Marrocco B, Pilotto S, Chittori S, Picaud S, Marchese S, Ciossani G, Forneris F, Filippakopoulos P, Schoehn G, Rhodes D, Subramaniam S, Mattevi A

Cell Rep. 27(2):387-399.e7. doi: 10.1016/j.celrep.2019.03.061

Publication date: April 9, 2019

PMID: 30970244

Bromodomain inhibition of the coactivators CBP/EP300 facilitate cellular reprogramming.

Ebrahimi A, Sevinç K, Gürhan Sevinç G, Cribbs AP, Philpott M, Uyulur F, Morova T, Dunford JE, Göklemez S, Arı Ş, Oppermann U, Önder TT

Nat. Chem. Biol.. doi: 10.1038/s41589-019-0264-z

Publication date: April 8, 2019

PMID: 30962627

A Parsimonious Mechanism of Sugar Dehydration by Human GDP-Mannose-4,6-dehydratase.

Pfeiffer M, Johansson C, Krojer T, Kavanagh KL, Oppermann U, Nidetzky B

ACS Catal. 9(4):2962-2968. doi: 10.1021/acscatal.9b00064

Publication date: April 5, 2019

PMID: 30984471

Substrate reduction therapy for inborn errors of metabolism.

Yue WW, Mackinnon S, Bezerra GA

Emerg Top Life Sci. 3(1):63-73. doi: 10.1042/ETLS20180058

Publication date: March 29, 2019

PMID: 33523197

Targeting bivalency de-represses Indian Hedgehog and inhibits self-renewal of colorectal cancer-initiating cells.

Lima-Fernandes E, Murison A, da Silva Medina T, Wang Y, Ma A, Leung C, Luciani GM, Haynes J, Pollett A, Zeller C, Duan S, Kreso A, Barsyte-Lovejoy D, Wouters BG, Jin J, Carvalho DD, Lupien M, Arrowsmith CH, O'Brien CA

Nat Commun. 10(1):1436. doi: 10.1038/s41467-019-09309-4

Publication date: March 29, 2019

PMID: 30926792

Crystal structure and activity-based labeling reveal the mechanisms for linkage-specific substrate recognition by deubiquitinase USP9X.

Paudel P, Zhang Q, Leung C, Greenberg HC, Guo Y, Chern YH, Dong A, Li Y, Vedadi M, Zhuang Z, Tong Y

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1815027116

Publication date: March 26, 2019

PMID: 30914461

AKT drives SOX2 overexpression and cancer cell stemness in esophageal cancer by protecting SOX2 from UBR5-mediated degradation.

Wang Z, Kang L, Zhang H, Huang Y, Fang L, Li M, Brown PJ, Arrowsmith CH, Li J, Wong J

Oncogene. doi: 10.1038/s41388-019-0790-x

Publication date: March 20, 2019

PMID: 30894683

Leveraging Compound Promiscuity to Identify Targetable Cysteines within the Kinome.

Rao S, Gurbani D, Du G, Everley RA, Browne CM, Chaikuad A, Li T, Schröder M, Gondi S, Ficarro SB, Sim T, Kim ND, Berberich MJ, Knapp S, Marto JA, Westover KD, Sorger PK, Gray NS

Cell Chem Biol. doi: 10.1016/j.chembiol.2019.02.021

Publication date: March 18, 2019

PMID: 30982749

Targeting the Small GTPase Superfamily through their Regulatory Proteins.

Gray JL, von Delft F, Brennan P

Angew. Chem. Int. Ed. Engl.. doi: 10.1002/anie.201900585

Publication date: March 14, 2019

PMID: 30869179

Divergent roles of prostacyclin and PGE2 in human tendinopathy.

Bergqvist F, Carr AJ, Wheway K, Watkins B, Oppermann U, Jakobsson PJ, Dakin SG

Arthritis Res. Ther.. 21(1):74. doi: 10.1186/s13075-019-1855-5

Publication date: March 13, 2019

PMID: 30867043

Solution structures and biophysical analysis of full-length group A PAKs reveal they are monomeric and auto-inhibited in cis.

Sorrell FJ, Kilian LM, Elkins JM

Biochem. J.. doi: 10.1042/BCJ20180867

Publication date: March 11, 2019

PMID: 30858169

Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder.

Roberts NA, Hilton EN, Lopes FM, Singh S, Randles MJ, Gardiner NJ, Chopra K, Coletta R, Bajwa Z, Hall RJ, Yue WW, Schaefer F, Weber S, Henriksson R, Stuart HM, Hedman H, Newman WG, Woolf AS

Kidney Int.. doi: 10.1016/j.kint.2018.11.040

Publication date: March 8, 2019

PMID: 30885509

Role of protein structure in variant annotation: structural insight of mutations causing 6-pyruvoyl-tetrahydropterin synthase deficiency.

Muniz JRC, Szeto NW, Frise R, Lee WH, Wang XS, Thöny B, Himmelreich N, Blau N, Hsiao KJ, Liu TT, Gileadi O, Oppermann U, Von Delft F, Yue WW, Tang NL

Pathology. doi: 10.1016/j.pathol.2018.11.011

Publication date: March 7, 2019

PMID: 30853107

Design and characterization of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems.

Harding RJ, Loppnau P, Ackloo S, Lemak A, Hutchinson A, Hunt B, Holehouse AS, Ho JC, Fan L, Toledo-Sherman L, Seitova A, Arrowsmith CH

J. Biol. Chem.. doi: 10.1074/jbc.RA118.007204

Publication date: March 6, 2019

PMID: 30842263

Organizational innovation for developing new medicines that target aging and age-related conditions.

Ford GA, Lord JM, Ferguson MA, Bountra C, Le Couteur DG

J. Gerontol. A Biol. Sci. Med. Sci.. doi: 10.1093/gerona/glz062

Publication date: March 6, 2019

PMID: 30838376

RNA interference may result in unexpected phenotypes in Caenorhabditis elegans.

De-Souza EA, Camara H, Salgueiro WG, Moro RP, Knittel TL, Tonon G, Pinto S, Pinca APF, Antebi A, Pasquinelli AE, Massirer KB, Mori MA

Nucleic Acids Res.. doi: 10.1093/nar/gkz154

Publication date: March 6, 2019

PMID: 30838421

A pharmacological master key mechanism that unlocks the selectivity filter gate in K+ channels.

Schewe M, Sun H, Mert Ü, Mackenzie A, Pike ACW, Schulz F, Constantin C, Vowinkel KS, Conrad LJ, Kiper AK, Gonzalez W, Musinszki M, Tegtmeier M, Pryde DC, Belabed H, Nazare M, de Groot BL, Decher N, Fakler B, Carpenter EP, Tucker SJ, Baukrowitz T

Science. 363(6429):875-880. doi: 10.1126/science.aav0569

Publication date: February 22, 2019

PMID: 30792303