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Crystal structure and kinetic analysis of β-lactamase inhibitor protein-II in complex with TEM-1 β-lactamase

Nature Structural Biology volume 8, pages 848–852 (2001)Cite this article

Abstract

The structure of the 28 kDa β-lactamase inhibitor protein-II (BLIP-II) in complex with the TEM-1 β-lactamase has been determined to 2.3 Å resolution. BLIP-II is a secreted protein produced by the soil bacterium Streptomyces exfoliatus SMF19 and is able to bind and inhibit TEM-1 with subnanomolar affinity. BLIP-II is a seven-bladed β-propeller with a unique blade motif consisting of only three antiparallel β-strands. The overall fold is highly similar to the core structure of the human regulator of chromosome condensation (RCC1). Although BLIP-II does not share the same fold with BLIP, the first β-lactamase inhibitor protein for which structural data was available, a comparison of the two complexes reveals a number of similarities and provides further insights into key components of the TEM-1–BLIP and TEM-1–BLIP-II interfaces. Our preliminary results from gene knock-out studies and scanning electron microscopy also reveal a critical role of BLIP-II in sporulation.

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Figure 1: Structure of the BLIP-II β-lactamase inhibitor protein.
Figure 2: TEM-1–BLIP-II interface.
Figure 3: TEM-1–BLIP interface.
Figure 4: Scanning electron micrographs of Streptomyces exfoliatus SMF19 cells.

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Acknowledgements

We thank S. Mosimann, Y. Luo and R. Pfuetzner for helpful suggestions and S. He for ESMS analysis. N.C.J.S. is supported by the Canadian Institutes of Health Research (Canada). K.J.L. is grateful to the KISTEP for a research grant from the International Joint R & D Project. N.C.J.S. is a CIHR scholar, a Burroughs Wellcome New Investigator and a HHMI International Scholar. D.L. is a recipient of a CIHR doctoral research award. S.G.K. is a recipient of a post-doctoral research award from the KOSEF.

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Author notes

  1. Daniel Lim, Hyeon Ung Park, Sung Gyun Kang, Hyun Sook Lee and Kye Joon Lee: Both authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of British, Columbia, Vancouver, Canada

    Daniel Lim, Liza De Castro & Natalie C.J. Strynadka

  2. Department of Biological Sciences, University of Alberta, Edmonton, Canada

    Hyeon Ung Park & Susan Jensen

  3. Department of Microbiology and Biotechnology, Graduate School of Biological Sciences, Seoul National University, Seoul, Korea

    Sung Gyun Kang, Hyun Sook Lee & Kye Joon Lee

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Correspondence to Kye Joon Lee or Natalie C.J. Strynadka.

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Lim, D., Park, H., De Castro, L. et al. Crystal structure and kinetic analysis of β-lactamase inhibitor protein-II in complex with TEM-1 β-lactamase. Nat Struct Mol Biol 8, 848–852 (2001). https://doi.org/10.1038/nsb1001-848

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