# Molecular Mechanisms, Pathways and Inhibition of Acetyl-Transfer Reactions

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2024 · $227,324

## Abstract

The goal of this administrative supplement of the parent award, R35GM118090, is to purchase a Prometheus
Panta from NANOTEMPER for the simultaneous detection of nano-Differential Scanning Fluorimetry
(nanoDSF), Backreflection, Dynamic Light Scattering (DLS) and Static Light Scattering (SLS). This instrument
overcomes many of the drawbacks of the current biophysical technologies available in the lab [Size Exclusion
Chromatography (SEC), Analytical Ultracentrifugation (AUC), Mass Photometry (MP), and Differential
Scanning Fluorimetry (DSF)], and will provide entirely new capabilities. The Prometheus Panta, requested in
this administrative supplement, will allow us to carry out protein and protein complex analysis rapidly,
accurately, label-free, and with low sample requirement of ~10 L at a wide range of protein and protein
complex concentrations of between 5 µg/mL – 250 mg/ml. This analysis will include protein and protein
complex quality assessment and buffer condition optimization for biochemical and structural (X-ray
crystallography and single particle cryo-EM) analysis, assessing thermal stability of protein, protein-ligand,
protein complexes and protein mutants as a readout for protein ligand binding and protein integrity,
respectively. Importantly, this technology will also provide entirely new capabilities to the lab including analysis
of samples in the presence of detergents and organic solvents, assessing molecular mass determinations at a
wide range of sample concentrations, and carrying out protein aggregation studies. The instrument also has
flexible throughput (24 samples using capillary chips or 48 samples when individual capillaries are loaded).
The instruments combined technologies comprised of nanoDSF, Backreflection, DLS, and SLS allow the
determination of key parameters including melting point (Tm), onset of unfolding temperature (Ton), turbidity
formation (Tturb), hydrodynamic radius (rH), self-interaction parameter (kD), polydispersity index (PDI), molecular
weight, and second virial coefficient (B22). Obtaining a Prometheus Panta will significantly advance the goals
and overall impact of the parent grant. Specific projects that will benefit from the instrumentation include
studies on multiprotein protein and RNA acetyltransferases (Sas2/4/5, Caf1 and Nat10), N-terminal protein
acetyltransferase (NAT) regulation (NAT complexes and ribosomes), small molecule acetyl-transfer enzymes
(ACLY, ACSS2, FASN, ACC1), inhibitor development (NatA, NatB, NatD, ACSS2, ACLY, FASN) and new
projects on membrane associated proteins (AANAT and HSD3B7). There is currently no comparable
instrument on campus or in the greater Philadelphia area. The instrument will be located in a dedicated
biophysical equipment room within the Marmorstein laboratory and Dr. Marmorstein’s home Department of
Biochemistry and Biophysics is committed to the proper installation and maintenance of the Mass Photometer
throughout its lifetime. Dr Marmorstein will also pro...

## Key facts

- **NIH application ID:** 11035886
- **Project number:** 3R35GM118090-09S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ronen Marmorstein
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $227,324
- **Award type:** 3
- **Project period:** 2016-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11035886

## Citation

> US National Institutes of Health, RePORTER application 11035886, Molecular Mechanisms, Pathways and Inhibition of Acetyl-Transfer Reactions (3R35GM118090-09S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11035886. Licensed CC0.

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