title: An evolutionary treasure: unification of a broad set of amidohydrolases related to urease.
abstract: The recent determination of the three-dimensional structure of urease revealed striking similarities of enzyme architecture to adenosine deaminase and phosphotriesterase, evidence of a distant evolutionary relationship that had gone undetected by one-dimensional sequence comparisons. Here, based on an analysis of conservation patterns in three dimensions, we report the discovery of the same active-site architecture in an even larger set of enzymes involved primarily in nucleotide metabolism. As a consequence, we predict the three-dimensional fold and details of the active site architecture for dihydroorotases, allantoinases, hydantoinases, AMP-, adenine and cytosine deaminases, imidazolonepropionase, aryldialkylphosphatase, chlorohydrolases, formylmethanofuran dehydrogenases, and proteins involved in animal neuronal development. Two member families are common to archaea, eubacteria, and eukaryota. Thirteen other functions supported by the same structural motif and conserved chemical mechanism apparently represent later adaptations for different substrate specificities in different cellular contexts.
authors.affiliation: European Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge, United Kingdom.
authors.forename: L
authors.initials: L
authors.lastname: Holm
authors.forename: C
authors.initials: C
authors.lastname: Sander
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D008024:Ligands; D019216:Metals, Heavy / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014510:Urease / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D008024:Ligands; D019216:Metals, Heavy; D000581:Amidohydrolases; D014510:Urease