William Gillette
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View article: Biophysical and structural analysis of KRAS switch-II pocket inhibitors reveals allele-specific binding constraints
Biophysical and structural analysis of KRAS switch-II pocket inhibitors reveals allele-specific binding constraints Open
RAS mutations are observed in 20% of all cancers, with the KRAS isoform highly mutated in colorectal, lung and pancreatic cancers. The last several years have seen the development of clinical compounds that target KRAS G12C mutations, with…
View article: Blocking C-terminal processing of KRAS4b via a direct covalent attack on the CaaX-box cysteine
Blocking C-terminal processing of KRAS4b via a direct covalent attack on the CaaX-box cysteine Open
RAS is the most frequently mutated oncogene in cancer. RAS proteins show high sequence similarities in their G-domains but are significantly different in their C-terminal hypervariable regions (HVR). These regions interact with the cell me…
View article: NMR 1H, 13C, and 15N resonance assignments of the oncogenic Q61R variant of human NRAS in the active, GTP-bound conformation
NMR 1H, 13C, and 15N resonance assignments of the oncogenic Q61R variant of human NRAS in the active, GTP-bound conformation Open
NRAS Q61R is a frequent mutation in melanoma. Hydrolysis of GTP by NRAS Q61R is reported to be much slower than other KRAS and NRAS mutants. Recent structural biology efforts for KRAS and NRAS proteins have been limited to X-ray crystallog…
View article: Producing recombinant proteins in Vibrio natriegens
Producing recombinant proteins in Vibrio natriegens Open
The diversity of chemical and structural attributes of proteins makes it inherently difficult to produce a wide range of proteins in a single recombinant protein production system. The nature of the target proteins themselves, along with c…
View article: Producing recombinant proteins in Vibrio natriegens
Producing recombinant proteins in Vibrio natriegens Open
The diversity of chemical and structural attributes of proteins makes it inherently difficult to produce a wide range of proteins in a single recombinant protein production system. The nature of the target proteins themselves, along with c…
View article: Thermal Shift Assay for Small GTPase Stability Screening: Evaluation and Suitability
Thermal Shift Assay for Small GTPase Stability Screening: Evaluation and Suitability Open
Thermal unfolding methods are commonly used as a predictive technique by tracking the protein’s physical properties. Inherent protein thermal stability and unfolding profiles of biotherapeutics can help to screen or study potential drugs a…
View article: Insights into the Cross Talk between Effector and Allosteric Lobes of KRAS from Methyl Conformational Dynamics
Insights into the Cross Talk between Effector and Allosteric Lobes of KRAS from Methyl Conformational Dynamics Open
KRAS is the most frequently mutated RAS protein in cancer patients, and it is estimated that about 20% of the cancer patients in the United States carried mutant RAS proteins. To accelerate therapeutic development, structures and dynamics …
View article: A humanized nanobody phage display library yields potent binders of SARS CoV-2 spike
A humanized nanobody phage display library yields potent binders of SARS CoV-2 spike Open
Neutralizing antibodies targeting the SARS-CoV-2 spike protein have shown a great preventative/therapeutic potential. Here, we report a rapid and efficient strategy for the development and design of SARS-CoV-2 neutralizing humanized nanobo…
View article: NMR 1H, 13C, 15N backbone resonance assignments of the T35S and oncogenic T35S/Q61L mutants of human KRAS4b in the active, GppNHp-bound conformation
NMR 1H, 13C, 15N backbone resonance assignments of the T35S and oncogenic T35S/Q61L mutants of human KRAS4b in the active, GppNHp-bound conformation Open
RAS proteins cycling between the active-form (GTP-bound) and inactive-form (GDP-bound) play a key role in cell signaling pathways that control cell survival, proliferation, and differentiation. Mutations at codon 12, 13, and 61 in RAS are …
View article: Undiagnosed SARS-CoV-2 seropositivity during the first 6 months of the COVID-19 pandemic in the United States
Undiagnosed SARS-CoV-2 seropositivity during the first 6 months of the COVID-19 pandemic in the United States Open
16.8 million SARS-CoV-2 infections in the US went undiagnosed in the first 6 months of the pandemic compared to 3.5 million diagnosed infections.
View article: Improved production of SARS-CoV-2 spike receptor-binding domain (RBD) for serology assays
Improved production of SARS-CoV-2 spike receptor-binding domain (RBD) for serology assays Open
The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a commonly used antigen for serology assays critical to determining the extent of SARS-CoV-2 exposure in the population. Different versions of the RBD protein have been d…
View article: Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane
Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane Open
Significance The proto-oncogene KRAS , a small GTPase, is frequently mutated in pancreatic, colorectal, and lung cancer. These mutations result in elevated levels of the activated guanosine triphosphate-bound form of KRAS. Localized at the…
View article: Optimizing high-yield production of SARS-CoV-2 soluble spike trimers for serology assays
Optimizing high-yield production of SARS-CoV-2 soluble spike trimers for serology assays Open
The SARS-CoV-2 spike trimer is the primary antigen for several serology assays critical to determining the extent of SARS-CoV-2 exposure in the population. Until stable cell lines are developed to increase the titer of this secreted protei…
View article: Homogeneous Dual-Parametric-Coupled Assay for Simultaneous Nucleotide Exchange and KRAS/RAF-RBD Interaction Monitoring
Homogeneous Dual-Parametric-Coupled Assay for Simultaneous Nucleotide Exchange and KRAS/RAF-RBD Interaction Monitoring Open
We have developed a rapid and sensitive single-well dual-parametric method introduced in linked RAS nucleotide exchange and RAS/RAF-RBD interaction assays. RAS mutations are frequent drivers of multiple different human cancers, but the dev…
View article: Biochemical and structural analyses reveal that the tumor suppressor neurofibromin (NF1) forms a high-affinity dimer
Biochemical and structural analyses reveal that the tumor suppressor neurofibromin (NF1) forms a high-affinity dimer Open
Neurofibromin is a tumor suppressor encoded by the NF1 gene, which is mutated in Rasopathy disease neurofibromatosis type I. Defects in NF1 lead to aberrant signaling through the RAS–mitogen-activated protein kinase pathway due to disrupti…
View article: Biochemical and structural analysis reveals the Neurofibromin (NF1) protein forms a high-affinity dimer
Biochemical and structural analysis reveals the Neurofibromin (NF1) protein forms a high-affinity dimer Open
Neurofibromin is the protein product of the NF1 gene which is mutated in the Rasopathy disease Neurofibromatosis Type I. Defects in NF1 lead to aberrant signaling through the RAS-MAPK pathway due to disruption of the Neurofibromin GTPase-a…
View article: Structures of N-terminally processed KRAS provide insight into the role of N-acetylation
Structures of N-terminally processed KRAS provide insight into the role of N-acetylation Open
Although post-translational modification of the C-terminus of RAS has been studied extensively, little is known about N-terminal processing. Mass spectrometric characterization of KRAS expressed in mammalian cells showed cleavage of the in…
View article: Quantitative biophysical analysis defines key components modulating recruitment of the GTPase KRAS to the plasma membrane
Quantitative biophysical analysis defines key components modulating recruitment of the GTPase KRAS to the plasma membrane Open
The gene encoding the GTPase KRAS is frequently mutated in pancreatic, lung, and colorectal cancers. The KRAS fraction in the plasma membrane (PM) correlates with activation of the mitogen-activated protein kinase (MAPK) pathway and subseq…
View article: Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies
Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies Open
Validation studies reveal the reliability of isoform- and mutation-specific anti-RAS antibodies.
View article: Structural basis of recognition of farnesylated and methylated KRAS4b by PDEδ
Structural basis of recognition of farnesylated and methylated KRAS4b by PDEδ Open
Significance Despite the significant progress made in the last few years toward targeting phosphodiesterase-δ (PDEδ) for KRAS (Kirsten rat sarcoma isoform)-driven cancers, there is no structural information available on posttranslationally…