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Fast product release requires active-site water dynamics in carbonic anhydrase

Author

Listed:
  • Jin Kyun Kim

    (Ulsan National Institute of Science and Technology (UNIST)
    Korea Research Institute of Standards and Science)

  • Seon Woo Lim

    (Ulsan National Institute of Science and Technology (UNIST))

  • Hannah Jeong

    (Ulsan National Institute of Science and Technology (UNIST))

  • Cheol Lee

    (Ulsan National Institute of Science and Technology (UNIST))

  • Seoyoon Kim

    (Ulsan National Institute of Science and Technology (UNIST))

  • Dong Woo Son

    (Gyeongsang National University
    Gyeongsang National University)

  • Rajeev Kumar

    (Pusan National University
    Pusan National University)

  • Jacob T. Andring

    (University of Florida)

  • Carrie Lomelino

    (University of Florida)

  • Jennifer L. Wierman

    (Ithaca)

  • Aina E. Cohen

    (Menlo Park)

  • Tae Joo Shin

    (Ulsan National Institute of Science and Technology (UNIST))

  • Cheol-Min Ghim

    (Ulsan National Institute of Science and Technology (UNIST))

  • Robert McKenna

    (University of Florida)

  • Byung Hoon Jo

    (Gyeongsang National University
    Gyeongsang National University
    Gyeongsang National University)

  • Duyoung Min

    (Ulsan National Institute of Science and Technology (UNIST))

  • Jeong-Mo Choi

    (Pusan National University
    Pusan National University)

  • Chae Un Kim

    (Ulsan National Institute of Science and Technology (UNIST))

Abstract

Water plays an essential role in enzyme structure, stability, and the substantial rate enhancement of enzyme catalysis. However, direct observations linking enzyme catalysis and active-site water dynamics pose a significant challenge due to experimental difficulties. By integrating an ultraviolet (UV) photolysis technique with temperature-controlled X-ray crystallography, we track the catalytic pathway of carbonic anhydrase II (CAII) at 1.2 Å resolution. This approach enables us to construct molecular movies of CAII catalysis, encompassing substrate (CO2) binding, conversion from substrate to product (bicarbonate), and product release. In the catalytic pathway, we identify an unexpected configuration in product binding and correlate it with sub-nanosecond rearrangement of active-site water. Based on these experimental observations, we propose a comprehensive mechanism of CAII and describe the detailed structure and dynamics of active-site water in CAII. Our findings suggest that CAII has evolved to utilize the structure and fast dynamics of the active-site waters for its diffusion-limited catalytic efficiency.

Suggested Citation

  • Jin Kyun Kim & Seon Woo Lim & Hannah Jeong & Cheol Lee & Seoyoon Kim & Dong Woo Son & Rajeev Kumar & Jacob T. Andring & Carrie Lomelino & Jennifer L. Wierman & Aina E. Cohen & Tae Joo Shin & Cheol-Min, 2025. "Fast product release requires active-site water dynamics in carbonic anhydrase," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59645-x
    DOI: 10.1038/s41467-025-59645-x
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    References listed on IDEAS

    as
    1. Katherine Henzler-Wildman & Dorothee Kern, 2007. "Dynamic personalities of proteins," Nature, Nature, vol. 450(7172), pages 964-972, December.
    2. Jin Kyun Kim & Cheol Lee & Seon Woo Lim & Aniruddha Adhikari & Jacob T. Andring & Robert McKenna & Cheol-Min Ghim & Chae Un Kim, 2020. "Elucidating the role of metal ions in carbonic anhydrase catalysis," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
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