15,956 Works

Data for paper 'Slip flow through channels with varying elliptic cross section'

Zachary Wilmott, Jon Chapman & Chris Breward

Quantitative mass imaging of single biological macromolecules

Philipp Kukura, Gavin Young & Nikolas Hundt

LEGEND-A clinical trial dataset

Ioannis Spiliotis

The FAIR Principles

FAIRsharing Team
One of the grand challenges of data-intensive science is to facilitate knowledge discovery by assisting humans and machines in their discovery of, access to, integration and analysis of, task-appropriate scientific data and their associated algorithms and workflows. Here, we describe FAIR - a set of guiding principles to make data Findable, Accessible, Interoperable, and Re-usable. These guidelines may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from...

Pleckstrin Homology Domain Interacting Protein (PHIP); A Target Enabling Package

Oakley Cox
SGC Oxford has expressed, purified and crystallized the second bromodomain of PHIP as part of the probe programme. Fragment screening and X-ray crystallography identified binders, some of which optimised to uM affinity. However, molecules with probe properties were not obtained. Consequently it has been decided to put the information generated into the public domain.

Lysine Demethylase JMJD2D (KDM4D); A Targeting Enabling Package

Paul Brennan
There are 4 members of the Lysine Demethylase JMJD2 (KDM4) family. SGC Oxford has expressed, purified and crystallized the catalytic domains of JMJD2A, JMJD2B, JMJD2C and JMJD2D as part of the probe programme. Fragment screening and X-ray crystallography identified a large number of binders, some of which were progressed into a medicinal chemistry programme. Despite significant effort molecules with probe properties were not obtained. Consequently it has been decided to put the information generated into...

Lysine Demethylase JMJD1B (KDM3B); A Target Enabling Package

Paul Brennan
There are 3 members of the Lysine Demethylase JMJD1 (KDM3) family, JMJD1A-C. SGC Oxford has expressed, purified and crystallized the catalytic domains of JMJD1A, JMJD1B and JMJD1C as part of the probe programme. Fragment screening and X-ray crystallography identified a large number of binders, some of which were progressed into a medicinal chemistry programme. Despite significant effort molecules with probe properties were not obtained. Consequently it has been decided to put the information generated into...

Supplementary Videos for Thesis

Valerio Pereno

GT-Predict

Charlie Fehl & Benjamin Davis
We utilized informatics and machine learning to build predictive software for enzyme functional annotation. The original application, GT-Predict, utilized the glycosyltransferase family 1 enzymes (GT1s) found in plants.

With No Lysine Kinase 3 (WNK3); A Target Enabling Package

Daniel Pinkas
Kinases WNK1-4 regulate cation-chloride cotransporters via phosphorylation of SPAK and OSR1 and thereby control salt homeostasis, cell volume and blood pressure. Gain of function mutations in WNK kinases are found in Gordon’s hypertension syndrome suggesting the WNK pathway as a therapeutic target. WNK3 inhibition in particular has also been shown to reduce cerebral injury after Ischemic stroke. Here we present assays and crystal structures that define (i) the molecular basis for disease mutations; (ii) the...

LIM Domain Kinase 1 (LIMK1), Human Kinase Domain; A Target Enabling Package

Sebastian Mathea
Loss of the translational repressor FMRP in fragile X syndrome causes upregulation of the type II BMP receptor BMPR2 and its non-canonical signalling via the kinase LIMK1. LIMK1 performs inhibitory phosphorylation on cofilin proteins blocking their actin-severing activity. Excessive BMPR2-LIMK1 activation was associated with dendritic spine and behavioural defects in animal models that could be rescued by BMPR2 knockdown or LIMK1 inhibition. Here we present a target enabling package for the therapeutic target LIMK1. We...

Cyclin-Dependent Kinase 12 (CDK12), Human Kinase Domain; A Target Enabling Package

Sarah Dixon-Clarke
Cyclin-dependent kinase 12 (CDK12) phosphorylates RNA Pol II C-terminal domain (CTD) to promote transcriptional elongation of large DNA damage response genes. CDK12 is frequently mutated or amplified in cancer and its loss sensitises cells to DNA damage. Here we present 3 crystal structures of the human CDK12/CycK complex including apo, AMP-PNP and covalent inhibitor complexes. Kinase assays compare domain truncations and report the Km values for substrate. THZ531 is presented as a potent and selective...

Human DNA Cross-Link Repair 1A (DCLRE1A, SNM1A); A Target Enabling Package

Joseph Newman
Cancer cells experience genomic instability, probably through a combination of excessive replicative activity and the loss of function of checkpoint and DNA repair pathways that may have contributed to the oncogenic transformation. Chemotherapy by DNA-damaging agents such as cisplatin and nitrogen mustards create DNA interstrand crosslinks (ICL), which can lead to double-strand breaks and cell death when the cells replicate their DNA. Genotoxic drugs are counteracted by the cell’s DNA damage response. Hence, it is...

Dolichyl-Phosphate Alpha-N-Acetyl Glucosaminyl Transferase (DPAGT1); A Target Enabling Package

Yin Dong
The ER integral membrane enzyme dolichyl-phosphate alpha-N-acetyl glucosaminyl phosphotransferase (DPAGT1) catalyses the first step in the synthesis of the oligosaccharide-P-P-dolichol unit which provides the glycans structure for N-glycosylation of proteins. Mutations in DPAGT1 cause two muscle weakness conditions, limb-girdle congenital myasthenic syndrome (CMS) and congenital disorder of glycosylation type 1j (CDG1j). DPAGT1 overexpression has also been implicated in oral cancer. We have produced and solved structures of this integral membrane enzyme, DPAGT1 with the V264G...

Human RECQL5 Helicase; A Target Enabling Package

Joseph Newman
RECQL5 is a member of the RecQ family of helicase which have important functions in DNA repair pathways and maintenance of genome integrity. RECQL5 has recently been identified as a synthetic lethal candidate in various haematological malignancies and has been verified by knockdown to sensitize myeloproliferative neoplasms (MPN) to DNA damaging agents. In this TEP we have expressed purified and determined the first ever crystal structures of RECQL5, in both APO and ADP/Mg2+ bound forms...

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