Open AccessStructural basis for the recognition of muramyltripeptide by Helicobacter pylori Csd4, a D,L‐carboxypeptidase controlling the helical cell shape
Author(s) -
Kim Hyoun Sook,
Kim Jieun,
Im Ha Na,
An Doo Ri,
Lee Mijoon,
Hesek Dusan,
Mobashery Shahriar,
Kim Jin Young,
Cho Kun,
Yoon Hye Jin,
Han Byung Woo,
Lee Byung Il,
Suh Se Won
Publication year - 2014
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s1399004714018732
Subject(s) - peptidoglycan , helicobacter pylori , carboxypeptidase , caga , cell wall , chemistry , biology , biochemistry , enzyme , virulence , genetics , gene
Helicobacter pylori infection causes a variety of gastrointestinal diseases, including peptic ulcers and gastric cancer. Its colonization of the gastric mucosa of the human stomach is a prerequisite for survival in the stomach. Colonization depends on its motility, which is facilitated by the helical shape of the bacterium. In H. pylori , cross‐linking relaxation or trimming of peptidoglycan muropeptides affects the helical cell shape. Csd4 has been identified as one of the cell shape‐determining peptidoglycan hydrolases in H. pylori . It is a Zn 2+ ‐dependent D,L‐carboxypeptidase that cleaves the bond between the γ‐D‐Glu and the m DAP of the non‐cross‐linked muramyltripeptide (muramyl‐L‐Ala‐γ‐D‐Glu‐ m DAP) of the peptidoglycan to produce the muramyldipeptide (muramyl‐L‐Ala‐γ‐D‐Glu) and m DAP. Here, the crystal structure of H. pylori Csd4 (HP1075 in strain 26695) is reported in three different states: the ligand‐unbound form, the substrate‐bound form and the product‐bound form. H. pylori Csd4 consists of three domains: an N‐terminal D,L‐carboxypeptidase domain with a typical carboxypeptidase fold, a central β‐barrel domain with a novel fold and a C‐terminal immunoglobulin‐like domain. The D,L‐carboxypeptidase domain recognizes the substrate by interacting primarily with the terminal m DAP moiety of the muramyltripeptide. It undergoes a significant structural change upon binding either m DAP or the m DAP‐containing muramyltripeptide. It it also shown that Csd5, another cell‐shape determinant in H. pylori , is capable of interacting not only with H. pylori Csd4 but also with the dipeptide product of the reaction catalyzed by Csd4.