FIGURE 1.

Sequence alignment of cNMP binding and acetyltransferase domains. A, multiple sequence alignment of the cNMP binding domains of Rv0998, MSMEG_5458, regulatory subunits of PKA (RIα, RIIα, and RIIβ), exchange protein activated by cAMP, hyperpolarization-activated cyclic nucleotide, and CRP from M. tuberculosis. The Protein Data Bank codes of structurally characterized proteins are shown. Asterisks represent important residues that are present in cNMP binding domains, which are discussed in the text. The black arrow represents the arginine (Arg-95 in MSMEG_5458) that is important for cAMP binding. Inset, a diagrammatic representation of the domain organization of MSMEG_5458/Rv0998. B, phylogenetic clustering of the cNMP binding domains in Rv0998 and MSMEG_5458. The gi numbers (supplemental Table S2, and in some cases, common names along with gi numbers) are shown, and A or B following the gi numbers identifies the first (N-terminal) or the second cNMP binding domain seen in the full-length protein sequences. PKA:A, cAMP binding domains in the regulatory subunits of PKA (A domain); GEF, guanine nucleotide exchange factor; PKA:B, cAMP binding domains in the regulatory subunits of PKA (B domain); PKG:A, cGMP binding domains in cGMP-dependent protein kinases (A domain); PKG:B, cGMP binding domains in cGMP-dependent protein kinases (B domain); CNG, cyclic nucleotide gated channels; NTE, neuropathy target esterase (also known as lysophospholipase NTE). Black dots indicate MSMEG_5458 and Rv0998. C, multiple sequence alignment of the acetyltransferase domain of Rv0998, MSMEG_5458, human GCN5 acetyltransferase, yeast histone acetyltransferase and tetrahymena GCN5 acetyltransferase. The Protein Data Bank codes of structurally characterized proteins are shown in the alignment. Asterisks represent important residues that are present in cNMP binding domains, which are discussed in the text. The black arrow identifies the glutamate residue important for acetyltransferase activity.