Publications | Structural Genomics Consortium

Autoantibodies against Four-and-a-Half-LIM Domain 1 (FHL1) in Inflammatory Myopathies: Results from an Australian Single-Center Cohort.

Galindo-Feria AS, Horuluoglu B, Day J, Fernandes-Cerqueira C, Wigren E, Gräslund S, Proudman S, Lundberg IE, Limaye V

Rheumatology (Oxford). doi: 10.1093/rheumatology/keac003

Publication date: January 12, 2022

Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells.

Baltzer S, Bulatov T, Schmied C, Krämer A, Berger BT, Oder A, Walker-Gray R, Kuschke C, Zühlke K, Eichhorst J, Lehmann M, Knapp S, Weston J, von Kries JP, Süssmuth RD, Klussmann E

Int J Mol Sci. 23(2):. doi: 10.3390/ijms23020763

Publication date: January 11, 2022

PMID: 35054947

Design of a Potent TLX Agonist by Rational Fragment Fusion.

Faudone G, Zhubi R, Celik F, Knapp S, Chaikuad A, Heering J, Merk D

J Med Chem. doi: 10.1021/acs.jmedchem.1c01757

Publication date: January 6, 2022

PMID: 34989568

TDP-43 Modulation by Tau-Tubulin Kinase 1 Inhibitors: A New Avenue for Future Amyotrophic Lateral Sclerosis Therapy.

Nozal V, Martínez-González L, Gomez-Almeria M, Gonzalo-Consuegra C, Santana P, Chaikuad A, Pérez-Cuevas E, Knapp S, Lietha D, Ramírez D, Petralla S, Monti B, Gil C, Martín-Requero A, Palomo V, de Lago E, Martinez A

J Med Chem. doi: 10.1021/acs.jmedchem.1c01942

Publication date: January 3, 2022

PMID: 34978799

Structural Aspects of LIMK Regulation and Pharmacology.

Chatterjee D, Preuss F, Dederer V, Knapp S, Mathea S

Cells. 11(1):. doi: 10.3390/cells11010142

Publication date: January 2, 2022

PMID: 35011704

Histone lysine methacrylation is a dynamic post-translational modification regulated by HAT1 and SIRT2.

Delaney K, Tan M, Zhu Z, Gao J, Dai L, Kim S, Ding J, He M, Halabelian L, Yang L, Nagarajan P, Parthun MR, Lee S, Khochbin S, Zheng YG, Zhao Y

Cell Discov. 7(1):122. doi: 10.1038/s41421-021-00344-4

Publication date: December 28, 2021

PMID: 34961760

Selective BH3 mimetics synergize with BET inhibition to induce mitochondrial apoptosis in rhabdomyosarcoma cells.

Erdogdu U, Dolgikh N, Laszig S, Särchen V, Meister MT, Wanior M, Knapp S, Boedicker C

Neoplasia. 24(2):109-119. doi: 10.1016/j.neo.2021.11.012

Publication date: December 23, 2021

PMID: 34959030

Prediction and Validation of a Protein's Free Energy Surface Using Hydrogen Exchange and (Importantly) Its Denaturant Dependence.

Peng X, Baxa M, Faruk N, Sachleben JR, Pintscher S, Gagnon IA, Houliston S, Arrowsmith CH, Freed KF, Rocklin GJ, Sosnick TR

J Chem Theory Comput. doi: 10.1021/acs.jctc.1c00960

Publication date: December 22, 2021

PMID: 34936354

Single tracer-based protocol for broad-spectrum kinase profiling in live cells with NanoBRET.

Robers MB, Wilkinson JM, Vasta JD, Berger LM, Berger BT, Knapp S

STAR Protoc. 2(4):100822. doi: 10.1016/j.xpro.2021.100822

Publication date: December 17, 2021

PMID: 34568844

Discovery of Novel BRD4 Ligand Scaffolds by Automated Navigation of the Fragment Chemical Space.

Piticchio SG, Martínez-Cartró M, Scaffidi S, Rachman M, Rodriguez-Arevalo S, Sanchez-Arfelis A, Escolano C, Picaud S, Krojer T, Filippakopoulos P, von Delft F, Galdeano C, Barril X

J Med Chem. doi: 10.1021/acs.jmedchem.1c01108

Publication date: December 13, 2021

PMID: 34898210

Structural basis for the recognition of the S2, S5-phosphorylated RNA polymerase II CTD by the mRNA anti-terminator protein hSCAF4.

Zhou M, Ehsan F, Gan L, Dong A, Li Y, Liu K, Min J

FEBS Lett. doi: 10.1002/1873-3468.14256

Publication date: December 13, 2021

PMID: 34897689

The Transcriptional Repressor Orphan Nuclear Receptor TLX Is Responsive to Xanthines.

Faudone G, Kilu W, Ni X, Chaikuad A, Sreeramulu S, Heitel P, Schwalbe H, Knapp S, Schubert-Zsilavecz M, Heering J, Merk D

ACS Pharmacol Transl Sci. 4(6):1794-1807. doi: 10.1021/acsptsci.1c00195

Publication date: December 10, 2021

PMID: 34927011

Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1.

Harding RJ, Deme JC, Hevler JF, Tamara S, Lemak A, Cantle JP, Szewczyk MM, Begeja N, Goss S, Zuo X, Loppnau P, Seitova A, Hutchinson A, Fan L, Truant R, Schapira M, Carroll JB, Heck AJR, Lea SM, Arrowsmith CH

Commun Biol. 4(1):1374. doi: 10.1038/s42003-021-02895-4

Publication date: December 8, 2021

PMID: 34880419

Exploration of Aberrant E3 Ligases Implicated in Alzheimer's Disease and Development of Chemical Tools to Modulate Their Function.

Potjewyd FM, Axtman AD

Front Cell Neurosci. 15:768655. doi: 10.3389/fncel.2021.768655

Publication date: December 7, 2021

PMID: 34867205

FOXN1 forms higher-order nuclear condensates displaced by mutations causing immunodeficiency.

Rota IA, Handel AE, Maio S, Klein F, Dhalla F, Deadman ME, Cheuk S, Newman JA, Michaels YS, Zuklys S, Prevot N, Hublitz P, Charles PD, Gkazi AS, Adamopoulou E, Qasim W, Davies EG, Hanson I, Pagnamenta AT, Camps C, Dreau HM, White A, James K, Fischer R, Gileadi O, Taylor JC, Fulga T, Lagerholm BC, Anderson G, Sezgin E, Holländer GA

Sci Adv. 7(49):eabj9247. doi: 10.1126/sciadv.abj9247

Publication date: December 3, 2021

PMID: 34860543

NUAK family kinase 2 is a novel therapeutic target for prostate cancer.

Fu W, Zhao MT, Driver LM, Schirmer AU, Yin Q, You S, Freedland SJ, DiGiovanni J, Drewry DH, Macias E

Mol Carcinog. doi: 10.1002/mc.23374

Publication date: November 24, 2021

PMID: 34818445

Structure-Based Design of Dual Partial Peroxisome Proliferator-Activated Receptor γ Agonists/Soluble Epoxide Hydrolase Inhibitors.

Lillich FF, Willems S, Ni X, Kilu W, Borkowsky C, Brodsky M, Kramer JS, Brunst S, Hernandez-Olmos V, Heering J, Schierle S, Kestner RI, Mayser FM, Helmstädter M, Göbel T, Weizel L, Namgaladze D, Kaiser A, Steinhilber D, Pfeilschifter W, Kahnt AS, Proschak A, Chaikuad A, Knapp S, Merk D, Proschak E

J Med Chem. doi: 10.1021/acs.jmedchem.1c01331

Publication date: November 24, 2021

PMID: 34818007

Inhibitors of the Hippo Pathway Kinases STK3/MST2 and STK4/MST1 Have Utility for the Treatment of Acute Myeloid Leukemia.

Bata N, Chaikuad A, Bakas NA, Limpert AS, Lambert LJ, Sheffler DJ, Berger LM, Liu G, Yuan C, Wang L, Peng Y, Dong J, Celeridad M, Layng F, Knapp S, Cosford NDP

J Med Chem. doi: 10.1021/acs.jmedchem.1c00804

Publication date: November 22, 2021

PMID: 34807584

Mutation in Abl kinase with altered drug-binding kinetics indicates a novel mechanism of imatinib resistance.

Lyczek A, Berger BT, Rangwala AM, Paung Y, Tom J, Philipose H, Guo J, Albanese SK, Robers MB, Knapp S, Chodera JD, Seeliger MA

Proc Natl Acad Sci U S A. 118(46):. doi: 10.1073/pnas.2111451118

Publication date: November 16, 2021

PMID: 34750265

A chemical probe targeting the PWWP domain alters NSD2 nucleolar localization.

Dilworth D, Hanley RP, Ferreira de Freitas R, Allali-Hassani A, Zhou M, Mehta N, Marunde MR, Ackloo S, Carvalho Machado RA, Khalili Yazdi A, Owens DDG, Vu V, Nie DY, Alqazzaz M, Marcon E, Li F, Chau I, Bolotokova A, Qin S, Lei M, Liu Y, Szewczyk MM, Dong A, Kazemzadeh S, Abramyan T, Popova IK, Hall NW, Meiners MJ, Cheek MA, Gibson E, Kireev D, Greenblatt JF, Keogh MC, Min J, Brown PJ, Vedadi M, Arrowsmith CH, Barsyte-Lovejoy D, James LI, Schapira M

Nat Chem Biol. doi: 10.1038/s41589-021-00898-0

Publication date: November 15, 2021

PMID: 34782742

Selectivity aspects of activity-based (chemical) probes.

Heinzlmeir S, Müller S

Drug Discov Today. doi: 10.1016/j.drudis.2021.10.021

Publication date: October 30, 2021

PMID: 34728376

The human pseudouridine synthase PUS7 recognizes RNA with an extended multi-domain binding surface.

Guegueniat J, Halabelian L, Zeng H, Dong A, Li Y, Wu H, Arrowsmith CH, Kothe U

Nucleic Acids Res. doi: 10.1093/nar/gkab934

Publication date: October 28, 2021

PMID: 34718722

Structural basis of the TAM domain of BAZ2A in binding to DNA or RNA independent of methylation status.

Chen S, Zhou M, Dong A, Loppnau P, Wang M, Min J, Liu K

J Biol Chem. 101351. doi: 10.1016/j.jbc.2021.101351

Publication date: October 26, 2021

PMID: 34715126

Design of a "Two-in-One" Mutant-Selective Epidermal Growth Factor Receptor Inhibitor That Spans the Orthosteric and Allosteric Sites.

Wittlinger F, Heppner DE, To C, Günther M, Shin BH, Rana JK, Schmoker AM, Beyett TS, Berger LM, Berger BT, Bauer N, Vasta JD, Corona CR, Robers MB, Knapp S, Jänne PA, Eck MJ, Laufer SA

J Med Chem. doi: 10.1021/acs.jmedchem.1c00848

Publication date: October 20, 2021

PMID: 34668706

Chemical Genetics Screen Identifies COPB2 Tool Compounds That Alters ER Stress Response and Induces RTK Dysregulation in Lung Cancer Cells.

Saraon P, Snider J, Schormann W, Rai A, Radulovich N, Sánchez-Osuna M, Coulombe-Huntington J, Huard C, Mohammed M, Lima-Fernandes E, Thériault B, Halabelian L, Chan M, Joshi D, Drecun L, Yao Z, Pathmanathan S, Wong V, Lyakisheva A, Aboualizadeh F, Niu L, Li F, Kiyota T, Subramanian R, Joseph B, Aman A, Prakesch M, Isaac M, Mamai A, Poda G, Vedadi M, Marcellus R, Uehling D, Leighl N, Sacher A, Samaržija M, Jakopović M, Arrowsmith C, Tyers M, Tsao MS, Andrews D, Al-Awar R, Stagljar I

J Mol Biol. 433(23):167294. doi: 10.1016/j.jmb.2021.167294

Publication date: October 16, 2021

PMID: 34662547

The structure of nontypeable Haemophilus influenzae SapA in a closed conformation reveals a constricted ligand-binding cavity and a novel RNA binding motif.

Lukacik P, Owen CD, Harris G, Bolla JR, Picaud S, Alibay I, Nettleship JE, Bird LE, Owens RJ, Biggin PC, Filippakopoulos P, Robinson CV, Walsh MA

PLoS One. 16(10):e0256070. doi: 10.1371/journal.pone.0256070

Publication date: October 16, 2021

PMID: 34653190

Structure-Activity Relationship of USP5 Inhibitors.

Mann MK, Zepeda-Velázquez CA, González-Álvarez H, Dong A, Kiyota T, Aman AM, Loppnau P, Li Y, Wilson B, Arrowsmith CH, Al-Awar R, Harding RJ, Schapira M

J Med Chem. doi: 10.1021/acs.jmedchem.1c00889

Publication date: October 14, 2021

PMID: 34648286

Discovery of a Potent and Highly Isoform-Selective Inhibitor of the Neglected Ribosomal Protein S6 Kinase Beta 2 (S6K2).

Gerstenecker S, Haarer L, Schröder M, Kudolo M, Schwalm MP, Wydra V, Serafim RAM, Chaikuad A, Knapp S, Laufer S, Gehringer M

Cancers (Basel). 13(20):. doi: 10.3390/cancers13205133

Publication date: October 13, 2021

PMID: 34680283

Synthesis and Evaluation of Novel 1,2,6-Thiadiazinone Kinase Inhibitors as Potent Inhibitors of Solid Tumors.

Kalogirou AS, East MP, Laitinen T, Torrice CD, Maffuid KA, Drewry DH, Koutentis PA, Johnson GL, Crona DJ, Asquith CRM

Molecules. 26(19):. doi: 10.3390/molecules26195911

Publication date: September 29, 2021

PMID: 34641454

Design and Development of a Chemical Probe for Pseudokinase Ca2+/calmodulin-Dependent Ser/Thr Kinase.

Russ N, Schröder M, Berger BT, Mandel S, Aydogan Y, Mauer S, Pohl C, Drewry DH, Chaikuad A, Müller S, Knapp S

J Med Chem. doi: 10.1021/acs.jmedchem.1c00845

Publication date: September 20, 2021

PMID: 34543009

Characterizing the role of the dark kinome in neurodegenerative disease - A mini review.

Axtman AD

Biochim Biophys Acta Gen Subj. 130014. doi: 10.1016/j.bbagen.2021.130014

Publication date: September 18, 2021

PMID: 34547390

Assessing reversible and irreversible binding effects of kinase covalent inhibitors through ADP-Glo assays.

Schröder M, Chaikuad A

STAR Protoc. 2(3):100717. doi: 10.1016/j.xpro.2021.100717

Publication date: September 17, 2021

PMID: 34401783

Development of a Selective Dual Discoidin Domain Receptor (DDR)/p38 Kinase Chemical Probe.

Röhm S, Berger BT, Schröder M, Chatterjee D, Mathea S, Joerger AC, Pinkas DM, Bufton JC, Tjaden A, Kovooru L, Kudolo M, Pohl C, Bullock AN, Müller S, Laufer S, Knapp S

J Med Chem. doi: 10.1021/acs.jmedchem.1c00868

Publication date: September 10, 2021

PMID: 34506142

Novel quaternary structures of the human prion protein globular domain.

Bortot LO, Rangel VL, Pavlovici FA, El Omari K, Wagner A, Brandao-Neto J, Talon R, von Delft F, Reidenbach AG, Vallabh SM, Minikel EV, Schreiber S, Nonato MC

Biochimie. 191:118-125. doi: 10.1016/j.biochi.2021.09.005

Publication date: September 10, 2021

PMID: 34517052

Discovery of a Potent Dual SLK/STK10 Inhibitor Based on a Maleimide Scaffold.

Serafim RAM, Sorrell FJ, Berger BT, Collins RJ, Vasconcelos SNS, Massirer KB, Knapp S, Bennett J, Fedorov O, Patel H, Zuercher WJ, Elkins JM

J Med Chem. doi: 10.1021/acs.jmedchem.0c01579

Publication date: August 31, 2021

PMID: 34463505

A NSD3-targeted PROTAC suppresses NSD3 and cMyc oncogenic nodes in cancer cells.

Xu C, Meng F, Park KS, Storey AJ, Gong W, Tsai YH, Gibson E, Byrum SD, Li D, Edmondson RD, Mackintosh SG, Vedadi M, Cai L, Tackett AJ, Kaniskan HÜ, Jin J, Wang GG

Cell Chem Biol. doi: 10.1016/j.chembiol.2021.08.004

Publication date: August 30, 2021

PMID: 34469831

Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer.

Schirmer AU, Driver LM, Zhao MT, Wells CI, Pickett JE, O'Bryne SN, Eduful BJ, Yang X, Howard L, You S, Devi GR, DiGiovanni J, Freedland SJ, Chi JT, Drewry DH, Macias E

Mol Ther. doi: 10.1016/j.ymthe.2021.08.029

Publication date: August 24, 2021

PMID: 34450249

Structural and functional characterization of ubiquitin variant inhibitors for the JAMM-family deubiquitinases STAMBP and STAMBPL1.

Guo Y, Liu Q, Mallette E, Caba C, Hou F, Fux J, LaPlante G, Dong A, Zhang Q, Zheng H, Tong Y, Zhang W

J Biol Chem. 101107. doi: 10.1016/j.jbc.2021.101107

Publication date: August 20, 2021

PMID: 34425109

Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase.

Newman JA, Douangamath A, Yadzani S, Yosaatmadja Y, Aimon A, Brandão-Neto J, Dunnett L, Gorrie-Stone T, Skyner R, Fearon D, Schapira M, von Delft F, Gileadi O

Nat Commun. 12(1):4848. doi: 10.1038/s41467-021-25166-6

Publication date: August 11, 2021

PMID: 34381037

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells.

Szewczyk MM, Vu V, Barsyte-Lovejoy D

J Vis Exp. doi: 10.3791/62418

Publication date: August 7, 2021

PMID: 34424246

Trends in kinase drug discovery: targets, indications and inhibitor design.

Attwood MM, Fabbro D, Sokolov AV, Knapp S, Schiöth HB

Nat Rev Drug Discov. doi: 10.1038/s41573-021-00252-y

Publication date: August 5, 2021

PMID: 34354255

Discovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors.

Henderson SH, Sorrell F, Bennett J, Fedorov O, Hanley MT, Godoi PH, Ruela de Sousa R, Robinson S, Ashall-Kelly A, Hopkins Navratilova I, Walter DS, Elkins JM, Ward SE

J Med Chem. doi: 10.1021/acs.jmedchem.1c01115

Publication date: August 3, 2021

PMID: 34342227

Identification of Pyrimidine-Based Lead Compounds for Understudied Kinases Implicated in Driving Neurodegeneration.

Drewry DH, Annor-Gyamfi JK, Wells CI, Pickett JE, Dederer V, Preuss F, Mathea S, Axtman AD

J Med Chem. doi: 10.1021/acs.jmedchem.1c00440

Publication date: August 1, 2021

PMID: 34333981

High-Throughput Crystallography Reveals Boron-Containing Inhibitors of a Penicillin-Binding Protein with Di- and Tricovalent Binding Modes.

Newman H, Krajnc A, Bellini D, Eyermann CJ, Boyle GA, Paterson NG, McAuley KE, Lesniak R, Gangar M, von Delft F, Brem J, Chibale K, Schofield CJ, Dowson CG

J Med Chem. doi: 10.1021/acs.jmedchem.1c00717

Publication date: July 31, 2021

PMID: 34337941

No shortcuts to SARS-CoV-2 antivirals.

Edwards A, Hartung IV

Science. 373(6554):488-489. doi: 10.1126/science.abj9488

Publication date: July 30, 2021

PMID: 34326222

Structure and Function of Protein Arginine Methyltransferase PRMT7.

Halabelian L, Barsyte-Lovejoy D

Life (Basel). 11(8):. doi: 10.3390/life11080768

Publication date: July 30, 2021

PMID: 34440512

The Small-Molecule Inhibitor MRIA9 Reveals Novel Insights into the Cell Cycle Roles of SIK2 in Ovarian Cancer Cells.

Raab M, Rak M, Tesch R, Gasimli K, Becker S, Knapp S, Strebhardt K, Sanhaji M

Cancers (Basel). 13(15):. doi: 10.3390/cancers13153658

Publication date: July 21, 2021

PMID: 34359562

Crystal Structure-Guided Design of Bisubstrate Inhibitors and Photoluminescent Probes for Protein Kinases of the PIM Family.

Nonga OE, Lavogina D, Enkvist E, Kestav K, Chaikuad A, Dixon-Clarke SE, Bullock AN, Kopanchuk S, Ivan T, Ekambaram R, Viht K, Knapp S, Uri A

Molecules. 26(14):. doi: 10.3390/molecules26144353

Publication date: July 19, 2021

PMID: 34299628

Production of Recombinant PRMT Proteins using the Baculovirus Expression Vector System.

Hutchinson A, Seitova A

J Vis Exp. doi: 10.3791/62510

Publication date: July 17, 2021

PMID: 34338677

Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes.

Eduful BJ, O'Byrne SN, Temme L, Asquith CRM, Liang Y, Picado A, Pilotte JR, Hossain MA, Wells CI, Zuercher WJ, Catta-Preta CMC, Zonzini Ramos P, Santiago AS, Couñago RM, Langendorf CG, Nay K, Oakhill JS, Pulliam TL, Lin C, Awad D, Willson TM, Frigo DE, Scott JW, Drewry DH

J Med Chem. doi: 10.1021/acs.jmedchem.0c02274

Publication date: July 15, 2021

PMID: 34264658