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Crystal structure of a phospholipase D family member

Nature Structural Biology volume 6, pages 278–284 (1999)Cite this article

Abstract

The first crystal structure of a phospholipase D (PLD) family member has been determined at 2.0 Å resolution. The PLD superfamily is defined by a common sequence motif, HxK(x)4D(x)6GSxN, and includes enzymes involved in signal transduction, lipid biosynthesis, endonucleases and open reading frames in pathogenic viruses and bacteria. The crystal structure suggests that residues from two sequence motifs form a single active site. A histidine residue from one motif acts as a nucleophile in the catalytic mechanism, forming a phosphoenzyme intermediate, whereas a histidine residue from the other motif appears to function as a general acid in the cleavage of the phosphodiester bond. The structure suggests that the conserved lysine residues are involved in phosphate binding. Large-scale genomic sequencing revealed that there are many PLD family members. Our results suggest that all of these proteins may possess a common structure and catalytic mechanism.

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Figure 1: Domain organization of the PLD superfamily of phosphodiesterases.
Figure 2: The PLD catalytic domain.
Figure 3: Bond interactions of the PLD consensus sequence.
Figure 4: The two-step catalytic mechanism of the PLD superfamily of phosphodiesterases.

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Acknowledgements

We would like to thank M. Ludwig and CHESS for providing synchrotron beam time, and J. Zhou and A. Metzger for technical support. This work was supported by a grant from the National Institutes of Health, NIDDK to J.E.D. and by the Walther Cancer Institute.

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  1. Department of Biological Chemistry, The University of Michigan, Ann Arbor, 48109-0606, Michigan, USA

    Jeanne A. Stuckey & Jack E. Dixon

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Correspondence to Jack E. Dixon.

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Stuckey, J., Dixon, J. Crystal structure of a phospholipase D family member. Nat Struct Mol Biol 6, 278–284 (1999). https://doi.org/10.1038/6716

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