# STRUCTURAL BASIS OF AMINORABINOSE BIOSYNTHESIS LINKED TO POLYMYXIN RESISTANCE

> **NIH NIH R00** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $249,000

## Abstract

Project Summary/Abstract
The research proposal outlined in this application is consisted of two components designed to facilitate the
transition of the principal investigator (PI) to an independent research career, a career development plan and a
research plan. The PI has a multidisciplinary background, and through this proposal, seeks to finalize his
training in Structural Biology of Membrane Proteins. The career development plan comprises a structured
educational experience for the first two years of the award (K99 phase) that includes training in Electron
Microscopy and Electron Paramagnetic Resonance (EPR) Spectroscopy for the study of Membrane Proteins,
and enhancement of career skills, such as grant writing, laboratory management, teaching and responsible
conduct of research. It includes a clear and actionable plan for identifying and successfully competing for an
independent tenure-track faculty position by the end of the K99 phase. The PI has assembled a multi-
disciplinary team of mentors, advisors and collaborators that will oversee and guide his training, research
program and transition to independence. The research plan spans both the mentored (K99) and independent
(R00) phases of the award. It involves mechanistic studies of the aminoarabinose sugar biosynthetic pathway
in Gram-negative bacteria that is linked to resistance to polymyxin-class antibiotics, our last line of defense
against multi-drug resistant infections. The research program for the K99 phase aims to build on knowledge
gained from a recent solution structure of an enzyme in the aminoarabinose pathway, named ArnT, by the PI
and his colleagues. The independent (R00) research program then aims to extend the structural studies to
other transmembrane enzymes of the aminoarabinose pathway, working towards a complete structural
description and functional characterization of the pathway. The core questions that the research program aims
to address are: (1) How does the enzyme ArnT accommodate its two lipidic substrates within the context of its
fold? (2) What are the molecular determinants that impart stereospecificity to some members of the ArnT
enzyme family but not others? (3) How is the ArnT enzyme changing during substrate binding and catalysis?
(4) How do the other transmembrane enzymes in the pathway look and how do they accomplish their
functions? (5) How do other transmembrane enzymes in the pathway accommodate the lipidic sugar carrier
undecaprenyl phosphate? To address these questions, the PI has put together a comprehensive research plan
that utilizes state-of-the-art methodologies. Moreover, the plan includes some technology development aimed
at extending the capabilities of electron microscopy within the context of the research program, and which,
upon completion of the program, may be applicable to other research programs. The proposed studies for the
K99 phase will largely take place in the prominent environment of Columbia University, which harbors a vibrant
...

## Key facts

- **NIH application ID:** 10017248
- **Project number:** 5R00GM123228-04
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Vasileios I Petrou
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2019-09-13 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017248

## Citation

> US National Institutes of Health, RePORTER application 10017248, STRUCTURAL BASIS OF AMINORABINOSE BIOSYNTHESIS LINKED TO POLYMYXIN RESISTANCE (5R00GM123228-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10017248. Licensed CC0.

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