Phosphatase Family CDC25

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Phosphatase Classification: Fold CC3 (Rhodanese): Superfamily CC3 (Rhodanese): Family CDC25

CDC25 consists of two subfamilies, CDC25 and Acr2. CDC25 is is an important phosphatase of cyclin-dependent kinases (CDKs), the function role of Acr2 is uncertain: it has arsenate reductase activity but may also be a protein phosphatase.

CDC25 and Acr2 are found in a largely exclusive clades. CDC25 is found in most animals, but is absent from plants, while Acr2 is found in plants but not animals. Most fungi and many protists have both.

Phosphatase domain structure

Compare the structures of CDC25 and Acr2 subfamilies

We compared the structures of three human CDC25s of CDC25 subfamily and yeast YCH1 of Acr2 subfamily.

The three human CDC25s have generally the same structure, which have a secondary structure (SS) combination of E1, H1, E2, H2, E3, E4, H3, E5, H4, E6, H5, E7. The strands E1, E2, E4, E5, E6 form a 5-stranded sheet; the strands E3 and E7 form a 2-stranded sheet.

The human CDC25s and yeast YCH1 share the SS elements of E1, H1, E2, E3, E4, H3, E5, H4, E6, H5, E7. But, yeast YCH1 structure is different from human CDC25s in two aspects:

  • While human CDC25s have an helix (H2) between E2 and E3, yeast YCH1 has an helix between E4 and H3. We named the SS elements as H2-YCH1.
  • Yeast YCH1 has a helix between H4 and E6. We name it as H4'-YCH1.

Note: We have the same SS annotation of CDC25 in the papers reported CDC25 structures [1, 2], but we have the SS annotation of YCH1 different from the paper reported its structure [3], where it had a SS elements of EHEEHHEHEH. We obtained the original annotations from DSSP and Stride programs and validated them in structure visualization.

Compare the structures of human CDC25s and Arabidopsis Acr2

Arabidopsis Acr2 has a solution NMR structure (PDB 1T3K). It lacks H1, E3 and E7. It also has slight difference in H3 localization.

References

  1. Fauman EB, Cogswell JP, Lovejoy B, Rocque WJ, Holmes W, Montana VG, Piwnica-Worms H, Rink MJ, and Saper MA. Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell. 1998 May 15;93(4):617-25. PubMed ID:9604936 | HubMed [Fauman98]
  2. Reynolds RA, Yem AW, Wolfe CL, Deibel MR Jr, Chidester CG, and Watenpaugh KD. Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle. J Mol Biol. 1999 Oct 29;293(3):559-68. DOI:10.1006/jmbi.1999.3168 | PubMed ID:10543950 | HubMed [Reynolds99]
  3. Yeo HK and Lee JY. Crystal structure of Saccharomyces cerevisiae Ygr203w, a homolog of single-domain rhodanese and Cdc25 phosphatase catalytic domain. Proteins. 2009 Aug 1;76(2):520-4. DOI:10.1002/prot.22420 | PubMed ID:19382206 | HubMed [Yeo09]
All Medline abstracts: PubMed | HubMed