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The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase.

Publication ,  Journal Article
Winger, JA; Derbyshire, ER; Lamers, MH; Marletta, MA; Kuriyan, J
Published in: BMC structural biology
October 2008

Soluble guanylate cyclases generate cyclic GMP when bound to nitric oxide, thereby linking nitric oxide levels to the control of processes such as vascular homeostasis and neurotransmission. The guanylate cyclase catalytic module, for which no structure has been determined at present, is a class III nucleotide cyclase domain that is also found in mammalian membrane-bound guanylate and adenylate cyclases.We have determined the crystal structure of the catalytic domain of a soluble guanylate cyclase from the green algae Chlamydomonas reinhardtii at 2.55 A resolution, and show that it is a dimeric molecule.Comparison of the structure of the guanylate cyclase domain with the known structures of adenylate cyclases confirms the close similarity in architecture between these two enzymes, as expected from their sequence similarity. The comparison also suggests that the crystallized guanylate cyclase is in an inactive conformation, and the structure provides indications as to how activation might occur. We demonstrate that the two active sites in the dimer exhibit positive cooperativity, with a Hill coefficient of approximately 1.5. Positive cooperativity has also been observed in the homodimeric mammalian membrane-bound guanylate cyclases. The structure described here provides a reliable model for functional analysis of mammalian guanylate cyclases, which are closely related in sequence.

Duke Scholars

Published In

BMC structural biology

DOI

EISSN

1472-6807

ISSN

1472-6807

Publication Date

October 2008

Volume

8

Start / End Page

42

Related Subject Headings

  • Sequence Alignment
  • Protein Structure, Tertiary
  • Protein Conformation
  • Molecular Sequence Data
  • Models, Molecular
  • Guanylate Cyclase
  • Enzyme Activation
  • Dimerization
  • Crystallography, X-Ray
  • Chlamydomonas reinhardtii
 

Citation

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Winger, J. A., Derbyshire, E. R., Lamers, M. H., Marletta, M. A., & Kuriyan, J. (2008). The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase. BMC Structural Biology, 8, 42. https://doi.org/10.1186/1472-6807-8-42
Winger, Jonathan A., Emily R. Derbyshire, Meindert H. Lamers, Michael A. Marletta, and John Kuriyan. “The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase.BMC Structural Biology 8 (October 2008): 42. https://doi.org/10.1186/1472-6807-8-42.
Winger JA, Derbyshire ER, Lamers MH, Marletta MA, Kuriyan J. The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase. BMC structural biology. 2008 Oct;8:42.
Winger, Jonathan A., et al. “The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase.BMC Structural Biology, vol. 8, Oct. 2008, p. 42. Epmc, doi:10.1186/1472-6807-8-42.
Winger JA, Derbyshire ER, Lamers MH, Marletta MA, Kuriyan J. The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase. BMC structural biology. 2008 Oct;8:42.
Journal cover image

Published In

BMC structural biology

DOI

EISSN

1472-6807

ISSN

1472-6807

Publication Date

October 2008

Volume

8

Start / End Page

42

Related Subject Headings

  • Sequence Alignment
  • Protein Structure, Tertiary
  • Protein Conformation
  • Molecular Sequence Data
  • Models, Molecular
  • Guanylate Cyclase
  • Enzyme Activation
  • Dimerization
  • Crystallography, X-Ray
  • Chlamydomonas reinhardtii