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Publication Abstract from PubMed

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 gamma-D-Glu and the mDAP of the non-cross-linked muramyltripeptide (muramyl-L-Ala-gamma-D-Glu-mDAP) of the peptidoglycan to produce the muramyldipeptide (muramyl-L-Ala-gamma-D-Glu) and mDAP. 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 beta-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 mDAP moiety of the muramyltripeptide. It undergoes a significant structural change upon binding either mDAP or the mDAP-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.

Structural basis for the recognition of muramyltripeptide by Helicobacter pylori Csd4, a D,L-carboxypeptidase controlling the helical cell shape.,Kim HS, Kim J, Im HN, An DR, Lee M, Hesek D, Mobashery S, Kim JY, Cho K, Yoon HJ, Han BW, Lee BI, Suh SW Acta Crystallogr D Biol Crystallogr. 2014 Nov;70(Pt 11):2800-12. doi:, 10.1107/S1399004714018732. Epub 2014 Oct 16. PMID:25372672^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.