8OWF

Clostridium perfringens chitinase CP4_3455 with chitosan

Summary for 8OWF

• Entry DOI: 10.2210/pdb8owf/pdb
• Related: 8C6Z 8OSE 8OTB 8OVR
• Descriptor: Chitodextrinase, 2-amino-2-deoxy-beta-D-glucopyranose-(1-4)-2-amino-2-deoxy-beta-D-glucopyranose-(1-4)-2-amino-2-deoxy-beta-D-glucopyranose-(1-4)-2-amino-2-deoxy-beta-D-glucopyranose-(1-4)-2-amino-2-deoxy-beta-D-glucopyranose-(1-4)-2-amino-2-deoxy-beta-D-glucopyranose, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: chitinase, necrotic enteritis, tim barrel, inhibitor, hydrolase
• Biological source: Clostridium perfringens
• Total number of polymer chains: 1
• Total formula weight: 66271.04

Authors

Bloch, Y.,Savvides, S.N. (deposition date: 2023-04-27, release date: 2023-07-12, Last modification date: 2024-11-13)

Primary citation

Dierick, E.,Callens, C.,Bloch, Y.,Savvides, S.N.,Hark, S.,Pelzer, S.,Ducatelle, R.,Van Immerseel, F.,Goossens, E.
Clostridium perfringens chitinases, key enzymes during early stages of necrotic enteritis in broiler chickens.
Plos Pathog., 20:e1012560-e1012560, 2024

PubMed Abstract: The interaction between bacteria and the intestinal mucus is crucial during the early pathogenesis of many enteric diseases in mammals. A critical step in this process employed by both commensal and pathogenic bacteria focuses on the breakdown of the protective layer presented by the intestinal mucus by mucolytic enzymes. C. perfringens type G, the causative agent of necrotic enteritis in broilers, produces two glycosyl hydrolase family 18 chitinases, ChiA and ChiB, which display distinct substrate preferences. Whereas ChiB preferentially processes linear substrates such as chitin, ChiA prefers larger and more branched substrates, such as carbohydrates presented by the chicken intestinal mucus. Here, we show via crystal structures of ChiA and ChiB in the apo and ligand-bound forms that the two enzymes display structural features that explain their substrate preferences providing a structural blueprint for further interrogation of their function and inhibition. This research focusses on the roles of ChiA and ChiB in bacterial proliferation and mucosal attachment, two processes leading to colonization and invasion of the gut. ChiA and ChiB, either supplemented or produced by the bacteria, led to a significant increase in C. perfringens growth. In addition to nutrient acquisition, the importance of chitinases in bacterial attachment to the mucus layer was shown using an in vitro binding assay of C. perfringens to chicken intestinal mucus. Both an in vivo colonization trial and a necrotic enteritis trial were conducted, demonstrating that a ChiA chitinase mutant strain was less capable to colonize the intestine and was hampered in its disease-causing ability as compared to the wild-type strain. Our findings reveal that the pathogen-specific chitinases produced by C. perfringens type G strains play a fundamental role during colonization, suggesting their potential as vaccine targets.

PubMed: 39283899
DOI: 10.1371/journal.ppat.1012560

Experimental method

X-RAY DIFFRACTION (1.3 Å)