Top Level Name
⌊ Superfamily (core) Amidohydrolase
|Total||=||Family known||+||Family unknown|
|Sequences of this superfamily were last updated on Sept. 4, 2013|
|New sequences were last added to this superfamily on April 26, 2012|
Enzymes in the amidohydrolase superfamily are related by their common partial reaction involving metal-assisted hydrolysis. In most cases, bound divalent metals at the active site activate water to a hydroxide which in turn acts as a nucleophile in the hydrolytic reaction. Conserved metal binding ligands serve as signatures within this highly diverse set of proteins. Reactions catalyzed by enzymes in this superfamily include deamination, dechlorination, dephosphorylation, decarboxylation, and isomerization. Enzymes in this superfamily contain a ellipsoidal TIM barrel structure with catalytic residues at the C-terminal ends of the beta strands. *This Superfamily is under curation. Family and Subgroup assignments are pending while we develop HMMs and define functional domain boundaries.
Holm, L. and C. Sander
An evolutionary treasure: unification of a broad set of amidohydrolases related to urease
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.
Seibert CM, Raushel FM
Structural and catalytic diversity within the amidohydrolase superfamily
The amidohydrolase superfamily comprises a remarkable set of enzymes that catalyze the hydrolysis of a wide range of substrates bearing amide or ester functional groups at carbon and phosphorus centers. The most salient structural landmark for this family of hydrolytic enzymes is a mononuclear or binuclear metal center embedded within the confines of a (beta/alpha)(8)-barrel structural fold. Seven variations in the identity of the specific amino acids that function as the direct metal ligands have been structurally characterized by X-ray crystallography. The metal center in this enzyme superfamily has a dual functionality in the expression of the overall catalytic activity. The scissile bond of the substrate must be activated for bond cleavage, and the hydrolytic water molecule must be deprotonated for nucleophilic attack. In all cases, the nucleophilic water molecule is activated through complexation with a mononuclear or binuclear metal center. In the binuclear metal centers, the carbonyl and phosphoryl groups of the substrates are polarized through Lewis acid catalysis via complexation with the beta-metal ion, while the hydrolytic water molecule is activated for nucleophilic attack by interaction with the alpha-metal ion. In the mononuclear metal centers, the substrate is activated by proton transfer from the active site, and the water is activated by metal ligation and general base catalysis. The substrate diversity is dictated by the conformational restrictions imposed by the eight loops that extend from the ends of the eight beta-strands.
Sequence Similarity Networks
Download a Sequence Similarity Network of this superfamily (XGMML format ).
Network downloads are XGMML files that are readable by program such as Cytoscape. In these networks, nodes represent proteins and edges represent pairwise similarities better than a given E-value cutoff. Additionally, these networks contain several attributes with data from the SFLD.
A detailed list of included node attributes, their definitions, and their uses is available here [revised: 11/20/2012].
Multiple Sequence Alignment
Multiple Sequence Alignment
Download full-length sequence sets of this superfamily as a FASTA format file.
Download annotation of sequences sets of this superfamily as a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application.
Some of these files can be quite large, please be patient during the download.
The maximum E-value at which pairwise similarities are included in the network.
Open in Cytoscape via:
→Network (multiple file types)