Phylogenetic Analysis and Molecular Evolution of Guanine Deaminases: From Guanine to Dendrites

Abstract

Guanine deaminase (GDA; guanase) is a ubiquitous enzyme that catalyzes the first step of purine metabolism by hydrolytic deamination of guanine, resulting in the production of xanthine. This hydrolase subfamily member plays an essential role in maintaining homeostasis of cellular triphosphate nucleotides for energy, signal transduction pathways, and nitrogen sources. In mammals, GDA protein levels can play a role in neuronal development by regulating dendritic arborization. We previously demonstrated that the most abundant alternative splice form of GDA in mammals, termed cypin (cytosolic PSD-95 interactor), interacts with postsynaptic density proteins, regulates microtubule polymerization, and increases dendrite number. Since purine metabolism and dendrite development were previously thought to be independent cellular processes, this multifunctional protein serves as a new target for the treatment of cognitive disorders characterized by aberrant neuronal morphology and purine metabolism. Although the enzymatic activity of GDA has been conserved during evolution from prokaryotes to higher eukaryotes, a detailed evolutionary assessment of the principal domains in GDA proteins has not yet been put forward. In this study, we perform a complete evolutionary analysis of the full-length sequences and the principal domains in guanine deaminases. Furthermore, we reconstruct the molecular phylogeny of guanine deaminases with neighbor-joining, maximum-likelihood, and UPGMA methods of phylogenetic inference. This study can act as a model whereby a universal housekeeping enzyme may be adapted to act also as a key regulator of a developmental process.

Gene Expression Profiling in Melasma in Korean Women

“…This is consistent with previous microarray reports that GDA was up-regulated by 3.087-fold in melasma skin lesions [9]. GDA is a ubiquitous enzyme that mediates the initial step of purine metabolism by the hydrolytic deamination of guanine, thus being involved in the synthesis of xanthine and tyrosine metabolism [28]. It is known that mammalian GDA plays a role in regulating dendritic arborization, thus being involved in neuronal development [29].…”

Plant Purine Nucleoside Catabolism Employs a Guanosine Deaminase Required for the Generation of Xanthosine in Arabidopsis

“…These conclusions are backed up by a phylogenetic analysis clearly separating the GDA and GSDA subfamilies and assigning the C. elegans and G. sulphuraria sequences to the GDA group ( Figure 5). Up to now, GDA of the cytidine/deoxycytidylate deaminase type has been documented only in prokaryotes (Fernández et al, 2009). …”

“…By contrast, GDA genes are well known, and the corresponding activity occurs in many organisms (Yuan et al, 1999;Maynes et al, 2000;Nygaard et al, 2000). There are two evolutionary origins for GDA (Nygaard et al, 2000;Fernández et al, 2009). The majority of species, including human and Escherichia coli, employ a protein that is member of the amidohydrolase family (Pfam profile PF01979), while a few prokaryotic organisms, including Bacillus subtilis, possess a protein belonging to the cytidine/deoxycytidylate deaminase family (Pfam profile PF00383).…”

Transcriptional Regulation of the Gene Cluster Encoding Allantoinase and Guanine Deaminase in Klebsiella pneumoniae

“…Sequence analysis of K. pneumoniae GuaD using a BLAST search showed that this protein has 86% identity with the proposed guanine deaminase of K. oxytoca and 58% identity with E. coli GuaD. The sequence includes the motif PGF VDAHVH between positions 73 and 81, which matches the consensus sequence implicated in metal binding (Zn 2ϩ ) in prokaryotic proteins of the cyclic amidohydrolase family (12). This motif is also present in K. oxytoca GuaD (28).…”