NlpC/p60 Peptidoglycan Hydrolase SagA Localizes to Sites of Cell Division and Requires Only a Catalytic Dyad for Protease Activity

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2020 Nov 2

PMID 33136372

Citations 4

Authors

Juliel Espinosa

Ti-Yu Lin

Yadyvic Estrella

Byungchul Kim

Henrik Molina

Howard C Hang

Affiliations

Soon will be listed here.

Abstract

Peptidoglycan is a vital component of the bacterial cell wall, and its dynamic remodeling by NlpC/p60 hydrolases is crucial for proper cell division and survival. Beyond these essential functions, we previously discovered that species express and secrete the NlpC/p60 hydrolase-secreted antigen A (SagA), whose catalytic activity can modulate host immune responses in animal models. However, the localization and peptidoglycan hydrolase activity of SagA in was still unclear. In this study, we show that SagA contributes to a triseptal structure in dividing cells of enterococci and localizes to sites of cell division through its N-terminal coiled-coil domain. Using molecular modeling and site-directed mutagenesis, we identify amino acid residues within the SagA-NlpC/p60 domain that are crucial for catalytic activity and potential substrate binding. Notably, these studies revealed that SagA may function via a catalytic Cys-His dyad instead of the predicted Cys-His-His triad, which is conserved in SagA orthologs from other species. Our results provide key additional insight into peptidoglycan remodeling in by SagA NlpC/p60 hydrolases.

Citing Articles

Secreted antigen A peptidoglycan hydrolase is essential for cell separation and priming of immune checkpoint inhibitor therapy.

Klupt S, Fam K, Zhang X, Chodisetti P, Mehmood A, Boyd T Elife. 2024; 13.

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Secreted antigen A peptidoglycan hydrolase is essential for cell separation and priming of immune checkpoint inhibitor therapy.

Klupt S, Fam K, Zhang X, Chodisetti P, Mehmood A, Boyd T bioRxiv. 2023; .

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Xie Y, Wang L, Yang Y, Zha L, Zhang J, Rong K Front Microbiol. 2023; 13:1071255.

PMID: 36590419 PMC: 9797508. DOI: 10.3389/fmicb.2022.1071255.

Peptidoglycan NlpC/P60 peptidases in bacterial physiology and host interactions.

Griffin M, Klupt S, Espinosa J, Hang H Cell Chem Biol. 2022; 30(5):436-456.

PMID: 36417916 PMC: 10192474. DOI: 10.1016/j.chembiol.2022.11.001.

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