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Two amino acid substitution convert a guanylyl cyclase, RetGC-1 into an adenylyl cyclase
- Source :
- Proceedings of the National Academy of Sciences of the United States. May 26, 1998, Vol. 95 Issue 11, p5993, 5 p.
- Publication Year :
- 1998
-
Abstract
- 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.
Details
- ISSN :
- 00278424
- Volume :
- 95
- Issue :
- 11
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.20857461