Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations.

Unlabelled: KRAS mutations are the most common genetic abnormalities in cancer, but the distribution of specific mutations across cancers and the differential responses of patients with specific KRAS mutations in therapeutic clinical trials suggest that different KRAS mutations have unique biochemical behaviors. To further explain these high-level clinical differences and to explore potential therapeutic strategies for specific KRAS isoforms, we characterized the most common KRAS mutants biochemically for substrate binding kinetics, intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activities, and interactions with the RAS effector, RAF kinase. Of note, KRAS G13D shows rapid nucleotide exchange kinetics compared with other mutants analyzed.

In situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C.

Directly targeting oncogenic V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras) with small-molecule inhibitors has historically been considered prohibitively challenging. Recent reports of compounds that bind directly to the K-Ras G12C mutant suggest avenues to overcome key obstacles that stand in the way of developing such compounds. We aim to target the guanine nucleotide (GN)-binding pocket because the natural contents of this pocket dictate the signaling state of K-Ras.

Investigating the deep supercooling ability of an Alaskan beetle, Cucujus clavipes puniceus, via high throughput proteomics.

Cucujus clavipes puniceus is a freeze avoiding beetle capable of surviving the long, extremely cold winters of the Interior of Alaska. Previous studies showed that some individuals typically supercool to mean values of approximately -40 °C, with some individuals supercooling to as low as -58 °C, but these non-deep supercooling (NDSC) individuals eventually freeze if temperatures drop below this. However, other larvae, especially if exposed to very cold temperatures, supercool even further.

Elucidating the biochemical overwintering adaptations of Larval Cucujus clavipes puniceus, a nonmodel organism, via high throughput proteomics.

Cucujus clavipes puniceus (C.c.p.

A cross-species compendium of proteins/gene products related to cold stress identified by bioinformatic approaches.

The purpose of this investigation was to construct a compendium of low temperature responsive proteins/gene products across species as identified by bioinformatics based approaches, thus allowing low temperature researchers a searchable database. Another purpose was to identify specific low temperature responsive proteins/gene products across at least two different species. We generated a database containing 2030 low temperature responsive protein/gene product entries, of which 1353 were up-regulated and 549 were down-regulated in response to various cold exposures across 34 different species; including bacteria (9 species), yeast (1 species), animals (including nematodes (1 species), collembola (2 species), insects (5 species), fish (1 species), amphibians (1 species), reptiles (1 species), mammals (2 species)), and plants (moss (1 species), gymnosperms (1 species) and angiosperms (9 species)).