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An evolutionary treasure: unification of a broad set of amidohydrolases related to urease

✍ Scribed by Liisa Holm; Chris Sander


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
429 KB
Volume
28
Category
Article
ISSN
0887-3585

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✦ Synopsis


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 onedimensional 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. Proteins 28:72-82, 1997