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Structure and metal exchange in the cadmium carbonic anhydrase of marine diatoms

Nature volume 452, pages 56–61 (2008)Cite this article

Abstract

Carbonic anhydrase, a zinc enzyme found in organisms from all kingdoms, catalyses the reversible hydration of carbon dioxide and is used for inorganic carbon acquisition by phytoplankton. In the oceans, where zinc is nearly depleted, diatoms use cadmium as a catalytic metal atom in cadmium carbonic anhydrase (CDCA). Here we report the crystal structures of CDCA in four distinct forms: cadmium-bound, zinc-bound, metal-free and acetate-bound. Despite lack of sequence homology, CDCA is a structural mimic of a functional β-carbonic anhydrase dimer, with striking similarity in the spatial organization of the active site residues. CDCA readily exchanges cadmium and zinc at its active site—an apparently unique adaptation to oceanic life that is explained by a stable opening of the metal coordinating site in the absence of metal. Given the central role of diatoms in exporting carbon to the deep sea, their use of cadmium in an enzyme critical for carbon acquisition establishes a remarkable link between the global cycles of cadmium and carbon.

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Figure 1: Structure of the second CA repeat of CDCA1 (CDCA1-R2).
Figure 2: CDCA1-R2 is a structural mimic of a functional dimer of β-CA.
Figure 3: Structure of CDCA1-R2 bound to substrate analogue acetate.
Figure 4: Facile metal exchange in CDCA1.
Figure 5: Structural basis of efficient metal exchange in CDCA1.
Figure 6: pH dependence of kcat/Km for the Cd-bound (circles) and Zn-bound (squares) CDCA1.

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Primary accessions

Protein Data Bank

Data deposits

Atomic coordinates have been deposited with the Protein Data Bank with the accession numbers 3BOB (R2-Cd), 3BOC (R2-Zn), 3BOE (R2-Cd-Acetate), 3BOH (R1-Cd-acetate) and 3BOJ (R1-metal free).

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Acknowledgements

We thank A. Saxena at the NSLS for assistance and Patrick McGinn for help with CA assays. This work was supported by start-up funds from Princeton University (to Y.S.), the NSF and the NSF-funded Center for Environmental Bioinorganic Chemistry (to F.M.M.M.).

Author Contributions Y.X. performed all the biochemical experiments; L.F. crystallized all forms of CDCA1; P.D.J. solved the structures; and F.M.M.M. and Y.S. supervised the work and wrote the paper. All authors discussed the results and commented on the manuscript.

Author information

Author notes

  1. Liang Feng

    Present address: Present address: Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York 10065, USA.,

  2. Yan Xu, Liang Feng and Philip D. Jeffrey: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Ecology and Evolutionary Biology,,

    Yan Xu

  2. Department of Molecular Biology,,

    Liang Feng, Philip D. Jeffrey & Yigong Shi

  3. Department of Geosciences, Princeton University, New Jersey 08544, USA,

    François M. M. Morel

Authors
  1. Yan Xu
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Corresponding authors

Correspondence to Yigong Shi or François M. M. Morel.

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Supplementary Information

The file contains Supplementary Tables 1-2 with the X-ray data statistics and Supplementary Figures 1-5 with Legends. (PDF 3573 kb)

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Xu, Y., Feng, L., Jeffrey, P. et al. Structure and metal exchange in the cadmium carbonic anhydrase of marine diatoms. Nature 452, 56–61 (2008). https://doi.org/10.1038/nature06636

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