A small step towards an important goal: fragment screen of the c-di-AMP-synthesizing enzyme CdaA

被引：1

作者：

Neumann, Piotr ^{[1
]}

Heidemann, Jana L. ^{[1
]}

Wollenhaupt, Jan ^{[2
]}

Dickmanns, Achim ^{[1
]}

Agthe, Michael ^{[3
]}

Weiss, Manfred S. ^{[2
]}

Ficner, Ralf ^{[1
,4
]}

机构：

[1] Georg August Univ Gottingen, Inst Microbiol & Genet, Dept Mol Struct Biol, GZMB, Justus von Liebig Weg 11, D-37077 Gottingen, Germany

[2] Helmholtz Zentrum Berlin, Macromol Crystallog, Albert Einstein Str 15, D-12489 Berlin, Germany

[3] Univ Hamburg, Inst Nanostruktur & Festko, Luruper Chaussee 149, D-22761 Hamburg, Germany

[4] Univ Gottingen, Cluster Excellence Multiscale Bioimaging Mol Mach, MBExC, D-37075 Gottingen, Germany

来源：

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY | 2024年 / 80卷

关键词：

crystallographic fragment screening; CdaA; Listeria monocytogenes; cyclic di-AMP; drug design; REFINEMENT; CHEMISTRY; DESIGN; MAPS;

D O I：

10.1107/S205979832400336X

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

CdaA is the most widespread diadenylate cyclase in many bacterial species, including several multidrug-resistant human pathogens. The enzymatic product of CdaA, cyclic di-AMP, is a secondary messenger that is essential for the viability of many bacteria. Its absence in humans makes CdaA a very promising and attractive target for the development of new antibiotics. Here, the structural results are presented of a crystallographic fragment screen against CdaA from Listeria monocytogenes, a saprophytic Gram-positive bacterium and an opportunistic food-borne pathogen that can cause listeriosis in humans and animals. Two of the eight fragment molecules reported here were localized in the highly conserved ATP-binding site. These fragments could serve as potential starting points for the development of antibiotics against several CdaA-dependent bacterial species.

引用

页码：350 / 361

页数：12