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

Journal Article · Sun Mar 01 04:00:00 EST 2015 · Acta Crystallographica. Section D: Biological Crystallography

DOI:https://doi.org/10.1107/S1399004715000152· OSTI ID:22347696

An, Doo Ri ^[1]; Kim, Hyoun Sook ^[1]; Kim, Jieun; Im, Ha Na; Yoon, Hye Jin; Yoon, Ji Young; Jang, Jun Young ^[1]; Hesek, Dusan; Lee, Mijoon; Mobashery, Shahriar ^[2]; Kim, Soon-Jong ^[3]; Lee, Byung Il ^[4]

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1. Seoul National University, Seoul 151-742 (Korea, Republic of)
2. University of Notre Dame, Notre Dame, IN 46556 (United States)
3. Mokpo National University, Chonnam 534-729 (Korea, Republic of)
4. National Cancer Center, Gyeonggi 410-769 (Korea, Republic of)

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. 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.

• OSTI ID: 22347696
• Journal Information: Acta Crystallographica. Section D: Biological Crystallography, Journal Name: Acta Crystallographica. Section D: Biological Crystallography Journal Issue: Pt 3 Vol. 71; ISSN ABCRE6; ISSN 0907-4449
• Country of Publication: Denmark
• Language: English

Related Subjects

75 CONDENSED MATTER PHYSICS
SUPERCONDUCTIVITY AND SUPERFLUIDITY
CHARGE DISTRIBUTION
CROSS-LINKING
CRYSTAL STRUCTURE
CRYSTALS
DISTRIBUTION
METALS
MODIFICATIONS
NEOPLASMS
SHAPE
SURFACES