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primary topic: Stoichiometry of ligand binding and role of C-terminal lysines in Mycobacterium tuberculosis and human GAPDH multifunctionality

Stoichiometry of ligand binding and role of C-terminal lysines in Mycobacterium tuberculosis and human GAPDH multifunctionality
type: AcademicArticle
type: Article
abstract: Glyceraldehyde-3-phosphate-dehydrogenase (GAPDH; EC1.2.1.12) has several functions in Mycobacterium tuberculosis (Mtb) and the human host. Apart from its role in glycolysis, it serves both as a cell surface and a secreted receptor for plasmin(ogen) (Plg/Plm), transferrin (Tf), and lactoferrin (Lf). Plg sequestration by Mtb GAPDH facilitates bacterial adhesion and tissue invasion, while an equivalent interaction with host GAPDH regulates immune cell migration. In both, host and microbe, internalization of Tf/Lf-GAPDH complexes serves as a route for iron acquisition. To date, the structure of Mtb GAPDH or the residues involved in these moonlighting interactions have not been identified. This study provides the first known X-ray crystal structure of Mtb GAPDH. Through further mutagenesis and functional assays, we found that the C-terminal lysines of Mtb and human GAPDH affect enzyme activity and ligand binding. We also establish the stoichiometry of Plg, Tf and Lf interactions with the GAPDH tetramer. Lastly, molecular simulation studies reveal the interactions of the C-terminal lysine residues.
date: 2024-12
volume: 291
issue: 23
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

FEBS J.
type: Collection

Subramanian Karthikeyan
type: Person
given name: Subramanian
family name: Karthikeyan

Sriraj Seth
type: Person
given name: Sriraj
family name: Seth

Rajender Kumar
type: Person
given name: Rajender
family name: Kumar

Adarsh Kumar
type: Person
given name: Adarsh
family name: Kumar

Manoj Raje
type: Person
given name: Manoj
family name: Raje

Ajay Kumar
type: Person
given name: Ajay
family name: Kumar

Chaaya Iyengar Raje
type: Person
given name: Chaaya
family name: Iyengar Raje

Himanshu Malhotra
type: Person
given name: Himanshu
family name: Malhotra

Vishant Mahendra Boradia
type: Person
given name: Vishant Mahendra
family name: Boradia

Prabha Garg
type: Person
given name: Prabha
family name: Garg

HTML Summary of #3321 Stoichiometry of ligand binding and role of C-terminal lysines in Mycobacterium tuberculosis and human GAPDH multifunctionality
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primary topic: Stoichiometry of ligand binding and role of C-terminal lysines in Mycobacterium tuberculosis and human GAPDH multifunctionality