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Title: Structure of Csd3 from Helicobacter pylori, a cell shape-determining metallopeptidase

H. pylori Csd3 (HP0506), together with other peptidoglycan hydrolases, plays an important role in determining cell shape. Its crystal structure in the latent state is reported. Helicobacter pylori is associated with various gastrointestinal diseases such as gastritis, ulcers and gastric cancer. Its colonization of the human gastric mucosa requires high motility, which depends on its helical cell shape. Seven cell shape-determining genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5 and csd6) have been identified in H. pylori. Their proteins play key roles in determining the cell shape through modifications of the cell-wall peptidoglycan by the alteration of cross-linking or by the trimming of peptidoglycan muropeptides. Among them, Csd3 (also known as HdpA) is a bifunctional enzyme. Its d, d-endopeptidase activity cleaves the d-Ala{sup 4}-mDAP{sup 3} peptide bond between cross-linked muramyl tetrapeptides and pentapeptides. It is also a d, d-carboxypeptidase that cleaves off the terminal d-Ala{sup 5} from the muramyl pentapeptide. Here, the crystal structure of this protein has been determined, revealing the organization of its three domains in a latent and inactive state. The N-terminal domain 1 and the core of domain 2 share the same fold despite a very low level of sequence identity, and their surface-charge distributions are different.more » The C-terminal LytM domain contains the catalytic site with a Zn{sup 2+} ion, like the similar domains of other M23 metallopeptidases. Domain 1 occludes the active site of the LytM domain. The core of domain 2 is held against the LytM domain by the C-terminal tail region that protrudes from the LytM domain.« less
Authors:
 [1] ;  [1] ;  [2] ; ; ; ; ;  [1] ; ; ;  [3] ;  [4] ;  [5] ;  [1] ;  [2]
  1. Seoul National University, Seoul 151-742 (Korea, Republic of)
  2. (Korea, Republic of)
  3. University of Notre Dame, Notre Dame, IN 46556 (United States)
  4. Mokpo National University, Chonnam 534-729 (Korea, Republic of)
  5. National Cancer Center, Gyeonggi 410-769 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22347696
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography; Journal Volume: 71; Journal Issue: Pt 3; Other Information: PMCID: PMC4356371; PMID: 25760614; PUBLISHER-ID: tz5068; OAI: oai:pubmedcentral.nih.gov:4356371; Copyright (c) An et al. 2015; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; CHARGE DISTRIBUTION; CROSS-LINKING; CRYSTAL STRUCTURE; CRYSTALS; DISTRIBUTION; METALS; MODIFICATIONS; NEOPLASMS; SHAPE; SURFACES