Tuesday December 9, 2025 – Michel Bertrand award – Yeganeh Habibi

Yeganeh Habibi, PhD

McGill University

2026 Michel Bertrand award recipient

 

 

 

 

 

Revealing the Structural Dynamics and Functional Properties of Class II Lanthipeptide Synthetases using Mass spectrometry-based techniques

 

Abstract

The widespread emergence of antibiotic-resistant bacteria has urged scientists to take immediate action to develop novel therapeutics and clinical practices. Most antibiotics used for medical purposes in humans are natural products that possess highly complex and ornate chemical structures. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a class of natural product peptides, with numerous biological functions, including antibiotic activity. Lanthipeptides, an emerging class of RiPPs, are sequentially modified by multifunctional enzyme(s) known as lanthipeptide synthetases that install a precise set of macrocycle rings into the peptide. Recent studies have suggested that conformational dynamics of enzyme-peptide complexes contribute to the high specificity of these enzymes. Here, we exploited number of mass spectrometry-based techniques to investigate the involvement of conformational changes in the model class II lanthipeptide synthetase, HalM2. We revealed that HalM2 is highly dynamic and identified structural elements involved in precursor peptide binding and allosteric communication. We also showed systematic conformational landscape changes in HalM2 in response to substrate modifications and revealed distinct leader and core peptide binding sites that independently alter HalM2 dynamics. This information can expand our fundamental knowledge about RiPP biosynthesis and ultimately assist in the design of catalysts that construct novel antibacterial compounds.

 

 

Biosketch

Yeganeh received her Ph.D. from McGill University in 2025 where she focused on understanding the dynamics and function of HalM2, an enzyme involved in biosynthesis of antibiotic natural product. Through her PhD, she developed a comprehensive hydrogen-deuterium exchange mass spectrometry (HDX-MS) workflow for probing HalM2 biophysical properties. Combined with number of MS-based techniques and biochemical assays, their study revealed unique sequence elements for substrate recognition, distinct from prior models, and mapped long-range structural communication in this enzyme class.

Date
Date(s) - December 9, 2025
6:00 pm - 8:00 pm

Emplacement / Location
Université de Montréal - Campus MIL (Beer and pizza at 18h, conference at 19h in A-4502)

Groupe de discussion en spectrométrie de masse de Montréal (GDSMM)

Le groupe de discussion sur la spectrométrie de masse de Montréal (GDSMM) est un organisme à but non lucratif qui offre un forum favorisant les interactions locales, nationales et internationales entre les scientifiques oeuvrant en spectrométrie de masse. Le GDSMM organise des séminaires scientifiques et des forums de discussion présentant les derniers développements en recherche fondamentale et appliquée en spectrométrie de masse. Une réunion annuelle du GDSMM qui regroupe les étudiants et les post-doctorants a lieu à Montréal chaque printemps et offre une opportunité unique de réseautage en plus d’accroitre la visibilité et la sensibilisation aux contributions locales en spectrométrie de masse.

Montreal mass spectrometry discussion group (MMSDG)

The Montreal mass spectrometry discussion group (MMSDG) is a not-for-profit organization that provides a forum to promote local, national and international interactions among scientists involved in mass spectrometry. MMSDG sponsors scientific seminars and forums to present the latest developments in basic and applied research in mass spectrometry. An annual MMSDG meeting that regroups students and postdoc is held every spring in Montreal, and provide a unique networking opportunity to participants and enhance the visibility and awareness of local contributions in mass spectrometry.