Statistical modelling and phylogenetic analysis of a deaminase domain.
Deamination reactions are catalyzed by a variety of enzymes including those involved in nucleoside/nucleotide metabolism and cytosine to uracil (C-->U) and adenosine to inosine (A-->I) mRNA editing. The active site of the deaminase (DM) domain in these enzymes contains a conserved histidine (or rarely cysteine), two cysteines and a glutamate proposed to act as a proton shuttle during deamination. Here, a statistical model, a hidden Markov model (HMM), of the DM domain has been created which identifies currently known DM domains and suggests new DM domains in viral, bacterial and eucaryotic proteins. However, no DM domains were identified in the currently predicted proteins from the archaeon Methanococcus jannaschii and possible causes for, and a potential means to ameliorate this situation are discussed. In some of the newly identified DM domains, the glutamate is changed to a residue that could not function as a proton shuttle and in one instance (Mus musculus spermatid protein TENR) the cysteines are also changed to lysine and serine. These may be non-competent DM domains able to bind but not act upon their substrate. Phylogenetic analysis using an HMM-generated alignment of DM domains reveals three branches with clear substructure in each branch. The results suggest DM domains that are candidates for yeast, platyhelminth, plant and mammalian C-->U and A-->I mRNA editing enzymes. Some bacterial and eucaryotic DM domains form distinct branches in the phylogenetic tree suggesting the existence of common, novel substrates.
Mian
I S
IS
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Moser
M J
MJ
Holley
W R
WR
Chatterjee
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites / Q000235:genetics; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics; D016208:Databases, Factual; D003641:Deamination; D004926:Escherichia coli / Q000201:enzymology*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D008390:Markov Chains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009700:Nucleoside Deaminases / Q000737:chemistry* / Q000235:genetics; D010802:Phylogeny; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment
D001426:Bacterial Proteins; D005656:Fungal Proteins; D010940:Plant Proteins; D009700:Nucleoside Deaminases; D003564:Cytidine Deaminase