Catalytic Features and Eradication Ability of Antibody Light-chain UA15-L against Helicobacter pylori

Emi Hifumi,Fumiko Morihara,Kenji Hatiuchi,Takuro Okuda,Akira Nishizono,Taizo Uda

doi:10.1074/jbc.m705674200

Emi Hifumi, Fumiko Morihara + Show 4 more

Open Access

https://doi.org/10.1074/jbc.m705674200

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Abstract

We have successfully developed a catalytic antibody capable of degrading the active site of the urease of Helicobacter pylori and eradicating the bacterial infection in a mouse stomach. This monoclonal antibody UA15 was generated using a designed recombinant protein UreB, which contained the crucial region of the H. pylori urease beta-subunit active site, for immunization. The light chain of this antibody (UA15-L) by itself showed a proteolytic activity to substantially degrade both UreB and the intact urease. Oral administration of UA15-L also significantly reduced the number of H. pylori in a mouse stomach. This is the first example of a monoclonal catalytic antibody capable of functioning in vivo, and such an antibody may have a therapeutic utility in the future.

Highlights

One of the potential utilities of catalytic antibodies is to use them for therapeutics, especially against the infectious agents, through the specific destruction of the essential proteins in a virus or bacteria
We have successfully developed a catalytic antibody capable of degrading the active site of the urease of Helicobacter pylori and eradicating the bacterial infection in a mouse stomach
H. pylori urease enables the bacterium to colonize the human stomach by neutralizing the acidic condition, through the conversion of urea into ammonium

Summary

Introduction

One of the potential utilities of catalytic antibodies is to use them for therapeutics, especially against the infectious agents, through the specific destruction of the essential proteins in a virus or bacteria. Have been reported in the past decade None of these catalytic antibodies have been developed into a therapeutic agent. A monoclonal catalytic antibody capable of destroying urease has a potential to be an effective therapeutic strategy to protect the stomach from the infection of H. pylori. One of the most important subjects in the study on catalytic antibody is whether or not we are able to prepare the catalytic antibody for the designated portion, which possesses the crucial function of the protein. A designed antigen (UreB), whose sequence is essential for the active site of the urease, was prepared and a catalytic antibody, UA15-L, was derived

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