title: Analysis of ancient sequence motifs in the H-PPase family.
abstract: The unique family of membrane-bound proton-pumping inorganic pyrophosphatases, involving pyrophosphate as the alternative to ATP, was investigated by characterizing 166 members of the UniProtKB/Swiss-Prot + UniProtKB/TrEMBL databases and available completed genomes, using sequence comparisons and a hidden Markov model based upon a conserved 57-residue region in the loop between transmembrane segments 5 and 6. The hidden Markov model was also used to search the approximately one million sequences recently reported from a large-scale sequencing project of organisms in the Sargasso Sea, resulting in additional 164 partial pyrophosphatase sequences. The strongly conserved 57-residue region was found to contain two nonapeptidyl sequences, mainly consisting of the four 'very early' proteinaceous amino acid residues Gly, Ala, Val and Asp, compatible with an ancient origin of the inorganic pyrophosphatases. The nonapeptide patterns have charged amino acid residues at positions 1, 5 and 9, are apparent binding sites for the substrate and parts of the active site, and were shown to be so specific for these enzymes that they can be used for functional assignments of unannotated genomes.
authors.affiliation: IFM Bioinformatics, Linköping University, Sweden.
authors.forename: Joel
authors.initials: J
authors.lastname: Hedlund
authors.forename: Roberto
authors.initials: R
authors.lastname: Cantoni
authors.forename: Margareta
authors.initials: M
authors.lastname: Baltscheffsky
authors.forename: Herrick
authors.initials: H
authors.lastname: Baltscheffsky
authors.forename: Bengt
authors.initials: B
authors.lastname: Persson
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D017124:Conserved Sequence; D030562:Databases, Protein; D019143:Evolution, Molecular; D020450:Heavy Ions; D043564:Inorganic Pyrophosphatase / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D012247:Rhodospirillum rubrum / Q000201:enzymology; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D043564:Inorganic Pyrophosphatase