All Outputs (19)

Characterisation of geranylgeranyl diphosphate synthase from the sandfly Lutzomyia longipalpis (2023)
Journal Article
Ducker, C., French, S., Pathak, M., Taylor, H., Sainter, A., Askem, W., …Oldham, N. J. (2023). Characterisation of geranylgeranyl diphosphate synthase from the sandfly Lutzomyia longipalpis. Insect Biochemistry and Molecular Biology, 161, Article 104001. https://doi.org/10.1016/j.ibmb.2023.104001

Leishmaniasis is a debilitating and often fatal neglected tropical disease. Males from sub-populations of the Leishmania-harbouring sandfly, Lutzomyia longipalpis, produce the diterpene sex and aggregation pheromone, sobralene, for which geranylgeran... Read More about Characterisation of geranylgeranyl diphosphate synthase from the sandfly Lutzomyia longipalpis.

Structures of factor XI and prekallikrein bound to domain 6 of high–molecular weight kininogen reveal alternate domain 6 conformations and exosites (2023)
Journal Article
Li, C., Barroeta, A. B., Wong, S. S., Kim, H. J., Pathak, M., Dreveny, I., …Emsley, J. (2023). Structures of factor XI and prekallikrein bound to domain 6 of high–molecular weight kininogen reveal alternate domain 6 conformations and exosites. Journal of Thrombosis and Haemostasis, https://doi.org/10.1016/j.jtha.2023.03.042

Background: High–molecular weight kininogen (HK) circulates in plasma as a complex with zymogen prekallikrein (PK). HK is both a substrate and a cofactor for activated plasma kallikrein, and the principal exosite interactions occur between PK N-termi... Read More about Structures of factor XI and prekallikrein bound to domain 6 of high–molecular weight kininogen reveal alternate domain 6 conformations and exosites.

Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase (2023)
Journal Article
Hicks, K. G., Cluntun, A. A., Schubert, H. L., Hackett, S. R., Berg, J. A., Leonard, P. G., …Rutter, J. (2023). Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase. Science, 379(6636), 996-1003. https://doi.org/10.1126/science.abm3452

Metabolic networks are interconnected and influence diverse cellular processes. The protein-metabolite interactions that mediate these networks are frequently low affinity and challenging to systematically discover. We developed mass spectrometry int... Read More about Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase.

Oncogenic deubiquitination controls tyrosine kinase signaling and therapy response in acute lymphoblastic leukemia (2022)
Journal Article
Jin, Q., Gutierrez Diaz, B., Pieters, T., Zhou, Y., Narang, S., Fijalkwoski, I., …Ntziachristos, P. (2022). Oncogenic deubiquitination controls tyrosine kinase signaling and therapy response in acute lymphoblastic leukemia. Science Advances, 8(49), https://doi.org/10.1126/sciadv.abq8437

Dysregulation of kinase signaling pathways favors tumor cell survival and therapy resistance in cancer. Here, we reveal a posttranslational regulation of kinase signaling and nuclear receptor activity via deubiquitination in T cell acute lymphoblasti... Read More about Oncogenic deubiquitination controls tyrosine kinase signaling and therapy response in acute lymphoblastic leukemia.

Next-Generation Phage Display to Identify Peptide Ligands of Deubiquitinases (2022)
Book Chapter
Spiliotopoulos, A., Maurer, S. K., Tsoumpeli, M. T., Bonfante, J. A. F., Owen, J. P., Gough, K. C., & Dreveny, I. (2023). Next-Generation Phage Display to Identify Peptide Ligands of Deubiquitinases. In J. Maupin-Furlow, & M. J. Edelmann (Eds.), Deubiquitinases: Methods and Protocols (189-218). Humana Press. https://doi.org/10.1007/978-1-0716-2803-4_12

Phage display (PD) is a powerful method and has been extensively used to generate monoclonal antibodies and identify epitopes, mimotopes, and protein interactions. More recently, the combination of next-generation sequencing (NGS) with PD (NGPD) has... Read More about Next-Generation Phage Display to Identify Peptide Ligands of Deubiquitinases.

Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair (2021)
Journal Article
Sanchez-Bailon, M. P., Choi, S. Y., Dufficy, E. R., Sharma, K., McNee, G. S., Gunnell, E., …Davies, C. C. (2021). Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair. Nature Communications, 12(1), Article 6313. https://doi.org/10.1038/s41467-021-26413-6

Cross-talk between distinct protein post-translational modifications is critical for an effective DNA damage response. Arginine methylation plays an important role in maintaining genome stability, but how this modification integrates with other enzym... Read More about Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair.

Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery (2020)
Journal Article
Kaira, B. G., Slater, A., McCrae, K. R., Dreveny, I., Sumya, U., Mutch, N. J., …Emsley, J. (2020). Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery. Blood, 136(14), 1685–1697. https://doi.org/10.1182/blood.2020004818

The contact system is composed of Factor XII (FXII), prekallikrein (PK) and co-factor kininogen (HK). The globular C1q receptor (gC1qR) has been shown to interact with FXII and HK. We reveal the FXII fibronectin type II domain (FnII) binds gC1qR in a... Read More about Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery.

Structural and biochemical evaluation of bisubstrate inhibitors of protein arginine N-methyltransferases PRMT1 and CARM1 (PRMT4) (2020)
Journal Article
Gunnell, E. A., Al-Noori, A., Muhsen, U., Davies, C. C., Dowden, J., & Dreveny, I. (2020). Structural and biochemical evaluation of bisubstrate inhibitors of protein arginine N-methyltransferases PRMT1 and CARM1 (PRMT4). Biochemical Journal, 477(4), 787–800. https://doi.org/10.1042/bcj20190826

Attenuating the function of protein arginine methyltransferases (PRMTs) is an objective for the investigation and treatment of several diseases including cardiovascular disease and cancer. Bisubstrate inhibitors that simultaneously target binding sit... Read More about Structural and biochemical evaluation of bisubstrate inhibitors of protein arginine N-methyltransferases PRMT1 and CARM1 (PRMT4).

Crystal structures of the recombinant β-factor XIIa protease with bound Thr-Arg and Pro-Arg substrate mimetics (2019)
Journal Article
Pathak, M., Manna, R., Li, C., Kaira, B. G., Hamad, B. K., Belviso, B. D., …Emsley, J. (2019). Crystal structures of the recombinant β-factor XIIa protease with bound Thr-Arg and Pro-Arg substrate mimetics. Acta Crystallographica. Section d, Structural Biology, 75(6), 578-591. https://doi.org/10.1107/s2059798319006910

© 2019 International Union of Crystallography. Coagulation factor XII (FXII) is a key initiator of the contact pathway, which contributes to inflammatory pathways. FXII circulates as a zymogen, which when auto-activated forms factor XIIa (FXIIa). Her... Read More about Crystal structures of the recombinant β-factor XIIa protease with bound Thr-Arg and Pro-Arg substrate mimetics.

Plasma kallikrein structure reveals apple domain disc rotated conformation compared to factor XI (2019)
Journal Article
Li, C., Voos, K. M., Pathak, M., Hall, G., McCrae, K. R., Dreveny, I., …Emsley, J. (2019). Plasma kallikrein structure reveals apple domain disc rotated conformation compared to factor XI. Journal of Thrombosis and Haemostasis, 17(5), 759-770. https://doi.org/10.1111/jth.14418

Background Plasma prekallikrein (PK) and factor XI (FXI) are apple domain‐containing serine proteases that when activated to PKa and FXIa cleave substrates kininogen, factor XII, and factor IX, respectively, directing plasma coagulation, bradykinin... Read More about Plasma kallikrein structure reveals apple domain disc rotated conformation compared to factor XI.

Discovery of peptide ligands targeting a specific ubiquitin-like domain– binding site in the deubiquitinase USP11 (2018)
Journal Article
Spiliotopoulos, A., Ferreras, L. B., Densham, R. M., Caulton, S. G., Maddison, B. C., Morris, J. R., …Dreveny, I. (2019). Discovery of peptide ligands targeting a specific ubiquitin-like domain– binding site in the deubiquitinase USP11. Journal of Biological Chemistry, 294(2), 424-436. https://doi.org/10.1074/jbc.RA118.004469

© 2019 Spiliotopoulos et al. Published by The American Society for Biochemistry and Molecular Biology, Inc. Ubiquitin-specific proteases (USPs) reverse ubiquitination and regulate virtually all cellular processes. Defined noncatalytic domains in USP... Read More about Discovery of peptide ligands targeting a specific ubiquitin-like domain– binding site in the deubiquitinase USP11.

The structure of the deubiquitinase USP15 reveals a misaligned catalytic triad and an open ubiquitin-binding channel (2018)
Journal Article
Ward, S. J., Gratton, H. E., Indrayudha, P., Michavila, C., Mukhopadhyay, R., Maurer, S. K., …Dreveny, I. (2018). The structure of the deubiquitinase USP15 reveals a misaligned catalytic triad and an open ubiquitin-binding channel. Journal of Biological Chemistry, 293(45), 17362-17374. https://doi.org/10.1074/jbc.RA118.003857

© 2018 Ward et al. Ubiquitin-specific protease 15 (USP15) regulates important cellular processes, including transforming growth factor β (TGF-β) signaling, mitophagy, mRNA processing, and innate immune responses; however, structural information on US... Read More about The structure of the deubiquitinase USP15 reveals a misaligned catalytic triad and an open ubiquitin-binding channel.

Identification of lipases with activity towards monoacylglycerol by criterion of conserved cap architectures (2018)
Journal Article
Riegler-Berket, L., Leitmeier, A., Aschauer, P., Dreveny, I., & Oberer, M. (in press). Identification of lipases with activity towards monoacylglycerol by criterion of conserved cap architectures. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1863(7),

Monoacylglycerol lipases (MGL) are a subclass of lipases that predominantly hydrolyze monoacylglycerol (MG) into glycerol and fatty acid. MGLs are ubiquitous enzymes across species and play a role in lipid metabolism, affecting energy homeostasis and... Read More about Identification of lipases with activity towards monoacylglycerol by criterion of conserved cap architectures.

PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism (2016)
Journal Article
Drees, S. L., Li, C., Prasetya, F., Saleem, M., Dreveny, I., Williams, P., …Fetzner, S. (2016). PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism. Journal of Biological Chemistry, 291(13), https://doi.org/10.1074/jbc.M115.708453

Pseudomonas aeruginosa produces a number of alkylquinolone-type secondary metabolites best known for their antimicrobial effects and involvement in cell-cell communication. In the alkylquinolone biosynthetic pathway, the β-ketoacyl-(acyl carrier prot... Read More about PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism.

Sensitive recovery of recombinant antibody clones after their in silico identification within NGS datasets (2015)
Journal Article
Spiliotopoulos, A., Owen, J. P., Maddison, B. C., Dreveny, I., Rees, H. C., & Gough, K. C. (2015). Sensitive recovery of recombinant antibody clones after their in silico identification within NGS datasets. Journal of Immunological Methods, 420, https://doi.org/10.1016/j.jim.2015.03.005

Recently the analytical power of the latest high throughput next generation DNA sequencing platforms has been used to analyse phage that have been selected from the panning of large combinatorial libraries displaying either peptide or antibody ligand... Read More about Sensitive recovery of recombinant antibody clones after their in silico identification within NGS datasets.

Coagulation factor XII protease domain crystal structure (2015)
Journal Article
Pathak, M., Wilmann, P., Awford, J., Li, C., Hamad, B., Fischer, P., …Emsley, J. (2015). Coagulation factor XII protease domain crystal structure. Journal of Thrombosis and Haemostasis, 13(4), 580-591. https://doi.org/10.1111/jth.12849

Background: Coagulation factor XII is a serine protease that is important for kinin generation and blood coagulation, cleaving the substrates plasma kallikrein and FXI. Objective: To investigate FXII zymogen activation and substrate recognition by d... Read More about Coagulation factor XII protease domain crystal structure.

Structural characterization of the apo form and NADH binary complex of human lactate dehydrogenase (2014)
Journal Article
Moses, J. E., Harper, S., Dempster, S., Dreveny, I., Harper, S., & Moses, J. (2014). Structural characterization of the apo form and NADH binary complex of human lactate dehydrogenase. Acta Crystallographica Section D: Biological Crystallography, 70(5), 1484-1490. https://doi.org/10.1107/s1399004714005422

Lactate dehydrogenase A (LDH-A) is a key enzyme in anaerobic respiration that is predominantly found in skeletal muscle and catalyses the reversible conversion of pyruvate to lactate in the presence of NADH. LDH-A is overexpressed in many tumours and... Read More about Structural characterization of the apo form and NADH binary complex of human lactate dehydrogenase.

Structure and Catalytic Regulatory Function of Ubiquitin Specific Protease 11 N-Terminal and Ubiquitin-like Domains (2014)
Journal Article
Harper, S., Gratton, H. E., Cornaciu, I., Oberer, M., Scott, D. J., Emsley, J., & Dreveny, I. (2014). Structure and Catalytic Regulatory Function of Ubiquitin Specific Protease 11 N-Terminal and Ubiquitin-like Domains. Biochemistry, 53(18), 2966-2978. https://doi.org/10.1021/bi500116x

The ubiquitin specific protease 11 (USP11) is implicated in DNA repair, viral RNA replication, and TGF? signaling. We report the first characterization of the USP11 domain architecture and its role in regulating the enzymatic activity. USP11 consists... Read More about Structure and Catalytic Regulatory Function of Ubiquitin Specific Protease 11 N-Terminal and Ubiquitin-like Domains.

The double PHD finger domain of MOZ/MYST3 induces ?-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification (2014)
Journal Article
Dreveny, I., Deeves, S. E., Fulton, J., Yue, B., Messmer, M., Bhattacharya, A., …Heery, D. M. (2014). The double PHD finger domain of MOZ/MYST3 induces α-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification. Nucleic Acids Research, 42(2), 822-835. https://doi.org/10.1093/nar/gkt931

Histone tail modifications control many nuclear processes by dictating the dynamic exchange of regulatory proteins on chromatin. Here we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine ac... Read More about The double PHD finger domain of MOZ/MYST3 induces ?-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification.