David Siderovski

Sweet Protein Allosteric Binding and Activation of the Human T1R2/R3 Sweet Receptor: A Simulation Model Validated by in Vitro Receptor Activation Assay Sweet proteins trigger sweet taste perception through interactions with the human T1R2/R3 sweet taste receptor. To date, relatively few proteins have been identified as causing sweet taste perception, and the four most studied proteins: monellin, brazzein, thaumatin, and honey truffle active component (HT-AC), have minimal sequence homology or structural similarities aside from positively charged surface sites. Sweet taste perception has also been found to be readily perturbed by minor changes in the protein structure, such as natural isoforms inherent to heterologous expression of the protein, and synthetic amino acid substitutions. This study uses ab initio rigid-body docking to predict the interactions of known sweet proteins and variants with a recently resolved cryo-EM structure of the T1R2/R3 sweet taste receptor, incorporating comparative analyses between apo-, holo-, and a potentially transient conformation of the receptor. HT-AC mediated activation of the sweet taste receptor is confirmed by in vitro cell-based assays, and results from in silico docking of various sweet proteins are used to derive additional insights regarding sweet taste perception. Perturbations of HT-AC due to naturally occurring post-translational modifications and synthetic modifications are evaluated using in vitro and in silico methods to determine robustness of the interaction between T1R2/R3 and sweet proteins with primary focuses on HT-AC.

This looks really cool… just bought some miracle fruit for the class to “play this game” live: Sweet Protein Allosteric Binding and Activation of the Human T1R2/R3 Sweet Receptor: A Simulation Model Validated by in Vitro Receptor Activation Assay | Biochemistry pubs.acs.org/doi/abs/10.1...

Proud of Percy Agogo-Mawuli getting his final dissertation chapter published (and equally proud of his leveraging of previously-unpublished "cool data" from our West Virginia colleagues all now on their own separate trajectories)... www.mdpi.com/1422-0067/26...

Developing inhibitors of the guanosine triphosphate hydrolysis accelerating activity of Regulator of G protein Signaling-14 www.biorxiv.org/content/10.1...
www.jbc.org/article/S002...

"Pouring one out" (audio-style) for the passing of my Teta...

Percy Agogo-Mawuli and David Siderovski in academic robes for UNTHSC 2025 graduation ceremonies

Congrats to Dr. Percy Agogo-Mawuli on his PhD completion on the topic of RGS12 in bipolar disorder! Off now to the Mayo Clinic asthma group for an exciting postdoc, working on the first human RGS gene I cloned back in 1987!

Heading off to the zen garden again this weekend.

A cat stares incredulously at a sleeping man…

Five am tornado warning sirens, you say? 🚨 🛌 😴

ChatGPT4o cites a seminal article on G protein beta/gamma subunits with an alleged co-author "Edward" Neer. WTF?

Description of OOF (painting from 1962 in the MoMA)

OOF (painting from 1962 in the MoMA)

Oh, AI? You got nothin' (yet) on us humans... It was Eva!

I am doubly concerned that this ChatGPT4o fork "Consensus" doesn't even realize it was the originator of this mistake from an earlier response to my prompt! OOF...

He’s so close to the Canadian border he could walk, but will likely drive :-) Get some Timmies too!

Bring me back some ketchup chips, eh? 🚨

Come for the science; leave with a bagel! (Or a meat raffle!)

The synthetic cannabinoid agonist WIN 55,212-2 reduces experimental pruritus via CB2 receptor activation - PubMed Pruritus (i.e., the experience that evokes a desire to scratch) is an adaptive process that can become maladaptive, leading to a persistent scratch-itch cycle that potentiates pruritus and increases t...

pubmed.ncbi.nlm.nih.gov/39551242/ 🧪📝🌿

Screenshot of abstract snippet from https://www.sciencedirect.com/science/article/abs/pii/S002839082400385X

When the first Delta8 flags 🚩🚩started appearing at every gas station on my route to campus, I just knew I had to scratch this research itch in cannabinoids! 🧪📝🌿 www.sciencedirect.com/science/arti...

Good on ya, mate! 🥯

Surface plasmon resonance (SPR) results from the binding of wildtype or R59Q-variant RGS12 PDZ domains to the C-terminal tail of SAPAP3.

Graphical abstract from recently published paper, indicating the location of the R59Q variation seen in the RGS12 PDZ domain that is associated with high-penetrance familial bipolar disorder.

So happy to see Percy Agogo-Mawuli finding new places where variations in RGS protein structure and function are implicated in disease states… 🧪 this time in high-penetrance familial bipolar disorder: pubmed.ncbi.nlm.nih.gov/39518985/

David Siderovski holding up four colored glowsticks while dressed for Halloween in a plastic Viking helmet.

Dear Dr. Monica, could I be added to the pharmacology & neuroscience Science-feed? Here are some of my credentials: en.Wikipedia.org/wiki/David_S... or orcid.org/0000-0002-06...

The museums of Fort Worth never fail to impress…

Happy Dominion Day! Only Canadian artists playing in the office today...

Endless rounds of rejiggering the academy's "corporate structure"? Not gonna grind me down!

ars technica article from 5/1/2024 announcing 60th anniversary of the BASIC programming language

Happy birthday!

ChatGPT4/DALL-E created an image of a human brain in a Petri dish.

David is horrified at the human brain image and send a comparison between a mouse brain and a human brain in response

ChatGPT4/DALL-E elevates the horror with an image of a literal "mouse-brain" with the limbs and snout and ears of a rodent but the body of a human brain (all in pink)

David complains and DALL-E again renders a human brain in a Petri dish

Yes, I am late to this finding, but I still find it hilarious, tragic, and often disturbing!

Bacillus cereus - Wikipedia

en.wikipedia.org/wiki/Bacillu... Cooked foods not meant for either immediate consumption or rapid cooling and refrigeration should be kept at temperatures below 10 °C (50 °F) or above 50 °C (122 °F).

Been a victim of this too many times...

Be serious.... I mean Bacillus cereus... ?!

We need a video of Clementine riding the robot-vacuum, please?!

Concluding statement from Coleman et al. (1994) Science 265:1405.

An oldie (30 years?!) but a goodie...

The registrar is waiting… ;-)

"Happy Christmas your arse" - a lament to his passing :-(

:-(

Yessir. Done.