title: Ancient conserved domains shared by animal soluble guanylyl cyclases and bacterial signaling proteins.
abstract: BACKGROUND
  Soluble guanylyl cyclases (SGCs) are dimeric enzymes that transduce signals downstream of nitric oxide (NO) in animals. They sense NO by means of a heme moiety that is bound to their N-terminal extensions.
  
  
  RESULTS
  Using sequence profile searches we show that the N-terminal extensions of the SGCs contain two globular domains. The first of these, the HNOB (Heme NO Binding) domain, is a predominantly alpha-helical domain and binds heme via a covalent linkage to histidine. Versions lacking this conserved histidine and are likely to interact with heme non-covalently. We detected HNOB domains in several bacterial lineages, where they occur fused to methyl accepting domains of chemotaxis receptors or as standalone proteins. The standalone forms are encoded by predicted operons that also contain genes for two component signaling systems and GGDEF-type nucleotide cyclases. The second domain, the HNOB associated (HNOBA) domain occurs between the HNOB and the cyclase domains in the animal SGCs. The HNOBA domain is also detected in bacteria and is always encoded by a gene, which occurs in the neighborhood of a gene for a HNOB domain.
  
  
  CONCLUSIONS
  The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals. The HNOBA domain functionally interacts with the HNOB domain, and possibly binds a ligand, either in cooperation, or independently of the latter domain. Phyletic profiles and phylogenetic analysis suggest that the HNOB and HNOBA domains were acquired by the animal lineage via lateral transfer from a bacterial source.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. lakshmin@ncbi.nlm.nih.gov
authors.forename: Lakshminarayan M
authors.initials: LM
authors.lastname: Iyer
authors.forename: Vivek
authors.initials: V
authors.lastname: Anantharaman
authors.forename: L
authors.initials: L
authors.lastname: Aravind
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001665:Binding Sites; D017124:Conserved Sequence; D019281:Dimerization; D006162:Guanylate Cyclase / Q000235:genetics* / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D009569:Nitric Oxide; D006418:Heme; D006162:Guanylate Cyclase