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Supramolecular assembly and acid resistance of Helicobacter pylori urease

Nature Structural Biology volume 8, pages 505–509 (2001)Cite this article

Abstract

Helicobacter pylori, an etiologic agent in a variety of gastroduodenal diseases, produces a large amount of urease, which is believed to neutralize gastric acid by producing ammonia for the survival of the bacteria. Up to 30% of the enzyme associates with the surface of intact cells upon lysis of neighboring bacteria. The role of the enzyme at the extracellular location has been a subject of controversy because the purified enzyme is irreversibly inactivated below pH 5. We have determined the crystal structure of H. pylori urease, which has a 1.1 MDa spherical assembly of 12 catalytic units with an outer diameter of ∼160 Å. Under physiologically relevant conditions, the activity of the enzyme remains unaffected down to pH 3. Activity assays under different conditions indicated that the cluster of the 12 active sites on the supramolecular assembly may be critical for the survival of the enzyme at low pH. The structure provides a novel example of a molecular assembly adapted for acid resistance that, together with the low Km value of the enzyme, is likely to enable the organism to inhabit the hostile niche.

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Figure 1: Structure of H. pylori urease.
Figure 2: Acid resistance of H. pylori urease.
Figure 3: The flap and the active site of H. pylori urease.

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Acknowledgements

The authors thank H. L. Mobley for the generous gift of the E. coli strain containing plasmids pHP808 and pHP902. We also thank the staff members at the Photon Factory beamline BL6A (Japan). We gratefully acknowledge the permission by T. J. Trust and the Journal of Bacteriology to use the TEM image of H. pylori urease as an inset in Fig. 1c. This study used the X-ray facility at Pohang Light Source (Korea) and was supported by Creative Research Initiatives of the Korean Ministry of Science and Technology and in part by a grant from Dong-Wha Pharmaceutical Co., Ltd.

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Authors and Affiliations

  1. Department of Life Science and Division of Molecular and Life Science, National Creative Research Initiative Center for Biomolecular Recognition, Pohang University of Science and Technology, Pohang, 790-784, Kyungbuk, Korea

    Nam-Chul Ha, Sang-Taek Oh, Jae Young Sung, Kyeung Ah Cha & Byung-Ha Oh

  2. College of Pharmacy, Catholic University of Daegu, Kyongsan, 712-702, Kyungbuk, Korea

    Mann Hyung Lee

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Correspondence to Byung-Ha Oh.

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Ha, NC., Oh, ST., Sung, J. et al. Supramolecular assembly and acid resistance of Helicobacter pylori urease. Nat Struct Mol Biol 8, 505–509 (2001). https://doi.org/10.1038/88563

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