The Cell Shape-determining Csd6 Protein from Helicobacter pylori Constitutes a New Family of l,d-Carboxypeptidase

Kim, Hyoun Sook; Im, Ha Na; An, Doo Ri; Yoon, Ji Young; Jang, Jun Young; Mobashery, Shahriar; Hesek, Dušan; Lee, Mijoon; Yoo, Jakyung; Cui, Minghua; Choi, Sun; Kim, Cheol-Hee; Lee, Nam Ki; Kim, Soon Jong; Kim, Jin Young; Bang, Geul; Han, Byung Woo; Lee, Byung Il; Yoon, Hye Jin; Suh, Se Won

doi:10.1074/jbc.m115.658781

Cited by 33 publications

(49 citation statements)

References 81 publications

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“…Treatment with a muramidase and HPLC analysis of the resulting fragments was used to uncover the substrate specificity of these enzymes. In one report, the synthetic compound β‐methyl MurNAc‐ l ‐Ala‐iso‐ d ‐Glu‐ meso ‐Dap‐ d ‐Ala was shown to act as a substrate for Csd6 from H. pylori , thus providing key evidence that the enzyme can act on small‐molecule substrates . Unfortunately, the lengthy synthesis of this compound makes it unattractive for use in further studies of mechanism or inhibitor design .…”

Section: Introductionmentioning

confidence: 75%

“…This manuscript focuses on Csd6 ( H. pylori ) and Pgp2 ( C. jejuni ), which catalyze the second step of the “trimming” process: the cleavage of d ‐Ala from the PG tetrapeptide to give a PG tripeptide (Scheme A) . Deletion of Csd6 or Pgp2 results in mutant bacteria with a straight‐rod morphology, impaired motility in a viscous medium, and reduced pathogenicity.…”

Section: Introductionmentioning

confidence: 99%

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Peptides Containing meso‐Oxa‐Diaminopimelic Acid as Substrates for the Cell‐Shape‐Determining Proteases Csd6 and Pgp2

et al. 2019

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Section: Introductionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Peptides Containing meso‐Oxa‐Diaminopimelic Acid as Substrates for the Cell‐Shape‐Determining Proteases Csd6 and Pgp2

et al. 2019

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“…We have recently reported the crystal structures of Csd6 (HP0518 in H . pylori 26695 strain) [ 28 ], Csd4 (HP1075) [ 29 ], and Csd3 (HP0506) [ 30 ]. We have shown that H .…”

Section: Introductionmentioning

confidence: 99%

Structural Basis of the Heterodimer Formation between Cell Shape-Determining Proteins Csd1 and Csd2 from Helicobacter pylori

Jang

et al. 2016

PLoS ONE

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Colonization of the human gastric mucosa by Helicobacter pylori requires its high motility, which depends on the helical cell shape. In H. pylori, several genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5, and csd6) play key roles in determining the cell shape by alteration of cross-linking or by trimming of peptidoglycan stem peptides. H. pylori Csd1, Csd2, and Csd3/HdpA are M23B metallopeptidase family members and may act as d,d-endopeptidases to cleave the d-Ala4-mDAP3 peptide bond of cross-linked dimer muropeptides. Csd3 functions also as the d,d-carboxypeptidase to cleave the d-Ala4-d-Ala5 bond of the muramyl pentapeptide. To provide a basis for understanding molecular functions of Csd1 and Csd2, we have carried out their structural characterizations. We have discovered that (i) Csd2 exists in monomer-dimer equilibrium and (ii) Csd1 and Csd2 form a heterodimer. We have determined crystal structures of the Csd2121–308 homodimer and the heterodimer between Csd1125–312 and Csd2121–308. Overall structures of Csd1125–312 and Csd2121–308 monomers are similar to each other, consisting of a helical domain and a LytM domain. The helical domains of both Csd1 and Csd2 play a key role in the formation of homodimers or heterodimers. The Csd1 LytM domain contains a catalytic site with a Zn2+ ion, which is coordinated by three conserved ligands and two water molecules, whereas the Csd2 LytM domain has incomplete metal ligands and no metal ion is bound. Structural knowledge of these proteins sheds light on the events that regulate the cell wall in H. pylori.

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“…The helical cell shape of H. pylori is generated and maintained by the peptidoglycan (PG) cell wall (16,17). PG-modifying enzymes (Csd1, Csd2, Csd3/HdpA, Csd4, and Csd6) are required to maintain helical cell shape in H. pylori (16)(17)(18)(19)(20)(21)(22). We and others have shown that H. pylori cell shape mutants (Δcsd1 curved-rod and Δcsd3 variably c-shapedrod mutants) are attenuated in stomach colonization (16,19).…”

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confidence: 99%

Nonhelical Helicobacter pylori Mutants Show Altered Gland Colonization and Elicit Less Gastric Pathology than Helical Bacteria during Chronic Infection

et al. 2019

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Half of all humans harbor Helicobacter pylori in their stomachs. Helical cell shape is thought to facilitate H. pylori’s ability to bore into the protective mucus layer in a corkscrew-like motion, thereby enhancing colonization of the stomach. H. pylori cell shape mutants show impaired colonization of the mouse stomach, highlighting the importance of cell shape in infection. To gain a deeper understanding of how helical cell morphology promotes host colonization by H. pylori, we used three-dimensional confocal microscopy to visualize the clinical isolate PMSS1 and an isogenic straight-rod mutant (Δcsd6) within thick longitudinal mouse stomach sections. We also performed volumetric image analysis to quantify the number of bacteria residing within corpus and antral glands in addition to measuring total CFU. We found that straight rods show attenuation during acute colonization of the stomach (1 day or 1 week postinfection) as measured by total CFU. Our quantitative imaging revealed that wild-type bacteria extensively colonized antral glands at 1 week postinfection, while csd6 mutants showed variable colonization of the antrum at this time point. During chronic infection (1 or 3 months postinfection), total CFU were highly variable but similar for wild-type and straight rods. Both wild-type and straight rods persisted and expanded in corpus glands during chronic infection. However, the straight rods showed reduced inflammation and disease progression. Thus, helical cell shape contributes to tissue interactions that promote inflammation during chronic infection, in addition to facilitating niche acquisition during acute infection.

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The Cell Shape-determining Csd6 Protein from Helicobacter pylori Constitutes a New Family of l,d-Carboxypeptidase

Cited by 33 publications

References 81 publications

Peptides Containing meso‐Oxa‐Diaminopimelic Acid as Substrates for the Cell‐Shape‐Determining Proteases Csd6 and Pgp2

Peptides Containing meso‐Oxa‐Diaminopimelic Acid as Substrates for the Cell‐Shape‐Determining Proteases Csd6 and Pgp2

Structural Basis of the Heterodimer Formation between Cell Shape-Determining Proteins Csd1 and Csd2 from Helicobacter pylori

Nonhelical Helicobacter pylori Mutants Show Altered Gland Colonization and Elicit Less Gastric Pathology than Helical Bacteria during Chronic Infection

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