Work

Structural Analysis of the Putative Succinyl-Diaminopimelic Acid Desuccinylase DapE from Campylobacter jejuni: Captopril-Mediated Structural Stabilization

Year: 2025

Type: article

Abstract: DapE is a highly conserved bacterial enzyme that produces L,L-diaminopimelic acid in the meso-diaminopimelic acid and lysine synthesis pathway, which is essential for peptidoglycan formation in the cell wall. DapE has been recognized as a promising antibacterial drug target and can be inhibited by captopril. The pathogenic bacterium Campylobacter jejuni expresses a DapE ortholog, cjDapE. However, the structural basis underlying the enzymatic activity of cjDapE and its inhibition by captopril is unknown. Here, we report the crystal structures of cjDapE in complexes with Zn2+ and with both Zn2+ and captopril. cjDapE consists of a catalytic domain (CD) and a dimerization domain (DD). The CD harbors a pocket, which accommodates two Zn2+ ions in close proximity as the catalytic active site. cjDapE assembles into a dimer primarily using DD residues, with two DD loops largely disordered in the absence of captopril. Upon captopril binding, these loops become ordered and contribute to dimer stabilization by involving both DD and CD residues. Notably, captopril binding maintains cjDapE in an open conformation that is incompatible with catalytic activity. Our comparative structural analysis suggests that captopril inhibits cjDapE primarily via substrate competition.

Source: Current Issues in Molecular Biology

DOI: 10.3390/cimb47121035

Authors: Si Yeon Ahn, Young-Bong You, Han Byeol Oh, Min-Ah Park, Sung-il Yoon

Institution: Kangwon National University

Language: English

Topic: Enzyme Structure and Function

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,654