George Lisi

About

The Lisi laboratory uses solution NMR methods along with techniques in biochemistry, biophysics, and molecular biology to interrogate changes in protein structure and conformational motions that underlie function. With a focus on enzyme complexes, we aim to understand how biological events such as protein-protein interaction or the binding of allosteric effectors and drugs modulate protein motion, intra- and intermolecular signaling, and/or catalytic activity.

Research topics

• Biochemistry
• Computer Science
• Biology
• Computational chemistry
• Genetics
• Biophysics
• Computational biology
• Chemistry

Selected publications

• High-throughput prediction of protein conformational distributions with subsampled AlphaFold2

  Nature Communications · 2024 · 179 citations

  This paper presents an innovative approach for predicting the relative populations of protein conformations using AlphaFold 2, an AI-powered method that has revolutionized biology by enabling the accurate prediction of protein structures. While AlphaFold 2 has shown exceptional accuracy and speed, it is designed to predict proteins' ground state conformations and is limited in its ability to predict conformational landscapes. Here, we demonstrate how AlphaFold 2 can directly predict the relative…

  DOI

• Principles of target DNA cleavage and the role of Mg2+ in the catalysis of CRISPR–Cas9

  Nature Catalysis · 2022 · 80 citations

  DOI

• Structural, biological, and biomedical implications of mRNA interactions with the master regulator HuR

  NAR Molecular Medicine · 2025-01-01 · 4 citations

  reviewOpen accessSenior author

  Human antigen R (HuR) is a ubiquitously expressed RNA-binding protein (RBP) that has been implicated in a vast range of biological processes including stress response, angiogenesis, cell proliferation, and differentiation. Dysregulation of HuR has been linked to a number of pathological disorders including vascular disease, inflammation, and cancers such as those of the breast and colon. Like many RBPs, HuR is composed of multiple RNA-recognition motif (RRM) domains; however, HuR and the three o…

  PublisherDOI

• Dynamic and structural insights into allosteric regulation on MKP5 a dual-specificity phosphatase

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-09-05 · 3 citations

  preprintOpen accessSenior authorCorresponding

  Dual-specificity mitogen-activated protein kinase (MAPK) phosphatases (MKPs) directly dephosphorylate and inactivate the MAPKs. Although the catalytic mechanism of dephosphorylation of the MAPKs by the MKPs is established, a complete molecular picture of the regulatory interplay between the MAPKs and MKPs still remains to be fully explored. Here, we sought to define the molecular mechanism of MKP5 regulation through an allosteric site within its catalytic domain. We demonstrate using crystallogr…

  PublisherDOI

• Dynamic and structural insights into allosteric regulation on MKP5 a dual-specificity phosphatase

  Nature Communications · 2025-07-31 · 2 citations

  articleOpen accessSenior author

  Dual-specificity mitogen-activated protein kinase (MAPK) phosphatases (MKPs) directly dephosphorylate and inactivate the MAPKs. Although the catalytic mechanism of dephosphorylation of the MAPKs by the MKPs is established, a complete molecular picture of the regulatory interplay between the MAPKs and MKPs still remains to be fully explored. Here, we sought to define the molecular mechanism of MKP5 regulation through an allosteric site within its catalytic domain. We demonstrate using crystallogr…

  PublisherOA PDFDOI

Recent grants

• BioMedical Big Data Core

  NIH · $45.2M · 2016–2026

• Unraveling the Allosteric Mechanism of Macrophage Migration Inhibitory Factor with Molecular Resolution

  NIH · $1.3M · 2022–2027

• CAREER: Molecular Resolution of Long-range Allostery in CRISPR-Cas9

  NSF · $1.4M · 2022–2026

Frequent coauthors

• Erin Skeens

  Providence College

  85 shared

• G. Jogl

  Target (United States)

  55 shared

• Helen B. Belato

  Providence College

  51 shared

• Alexandra M. D’Ordine

  Providence College

  46 shared

• Víctor S. Batista

  Yale University

  42 shared

• Giulia Palermo

  37 shared

• Jennifer Y. Cui

  Providence College

  30 shared

• Kyle W. East

  Brown University

  27 shared

Labs

• Lisi Lab at Brown UniversityPI

  The Lisi lab studies the biochemistry and structural biology of enzyme and nucleic acid complexes.

Similar researchers at Brown University

• Weihan Lih-83
• Eric Morrowh-76
• Mark Johnsonh-75