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Two amino acid substitutions convert a guanylyl cyclase, RetGC-1, into an adenylyl cyclase
Open accessAbstract
Guanylyl cyclases (GCs) and adenylyl cyclases (ACs) have fundamental roles in a wide range of cellular processes. Whereas GCs use GTP as a substrate to form cGMP, ACs catalyze the analogous conversion of ATP to cAMP. Previously, a model based on the structure of adenylate cyclase was used to predict the structure of the nucleotide-binding pocket of a membrane guanylyl cyclase, RetGC-1. Based on this model, we replaced specific amino acids in the guanine-binding pocket of GC with their counterparts from AC. A change of two amino acids, E925K together with C995D, is sufficient to completely alter the nucleotide specificity from GTP to ATP. These experiments strongly validate the AC-derived RetGC-1 structural model and functionally confirm the role of these residues in nucleotide discrimination.
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Cited by
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Leber congenital amaurosis: Genes, proteins and disease mechanisms
den Hollander, A. I., Roepman, R., Koenekoop, R. K., & Cremers, F. P. M. (2008) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2008.05.003 · Cited by 811
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Sunahara, R. K. (2002) · Molecular Interventions · doi:10.1124/mi.2.3.168 · Cited by 406
Allosteric Control of Cyclic di-GMP Signaling
Christen, B., Christen, M., Paul, R., Schmid, F., Folcher, M., Jenoe, P., Meuwly, M., & Jenal, U. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603589200 · Cited by 294
Metadata
- Authors
- Tucker, C. L., Hurley, J. H., Miller, T. R., & Hurley, J. B.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-05-26
- Volume
- 95
- Issue
- 11
- Pages
- 5993-5997
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2010730039
- Cited by
- 215
- References
- 0
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Two amino acid substitutions convert a guanylyl cyclase, RetGC-1, into an adenylyl cyclase. https://app.cochat.ai/papers/10.1073/pnas.95.11.5993
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- Tucker, C. L., Hurley, J. H., Miller, T. R., & Hurley, J. B. (1998). Two amino acid substitutions convert a guanylyl cyclase, RetGC-1, into an adenylyl cyclase. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.95.11.5993
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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