text: The first class of adenylyl cyclases occur in many bacteria including E. coli (as CyaA  [unrelated to the Class II enzyme]). This was the first class of AC to be characterized. It was observed that E. coli deprived of glucose produce cAMP that serves as an internal signal to activate expression of genes for importing and metabolizing other sugars. cAMP exerts this effect by binding the transcription factor CRP, also known as CAP. Class I AC's are large cytosolic enzymes (~100 kDa) with a large regulatory domain (~50 kDa) that indirectly senses glucose levels. , no crystal structure is available for class I AC.
  Some indirect structural information is available for this class. It is known that the N-terminal half is the catalytic portion, and that it requires two Mg ions. S103, S113, D114, D116 and W118 are the five absolutely essential residues. The class I catalytic domain () belongs to the same superfamily () as the palm domain of DNA polymerase beta (). Aligning its sequence onto the structure onto a related archaeal CCA tRNA nucleotidyltransferase () allows for assignment of the residues to specific functions: γ-phosphate binding, structural stabilization, DxD motif for metal ion binding, and finally ribose binding.