Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monofunctional histidinol phosphate phosphatase from Thermus thermophilus HB8, which catalyzes the dephosphorylation of l-histidinol phosphate, belongs to the PHP family, together with the PHP domain of bacterial DNA polymerase III and family X DNA polymerase. We have determined the structures of the complex with a sulfate ion, the complex with a phosphate ion, and the unliganded form at 1.6, 2.1, and 1.8 A resolution, respectively. The enzyme exists as a tetramer, and the subunit consists of a distorted (betaalpha)7 barrel with one linker and one C-terminal tail. Three metal sites located on the C-terminal side of the barrel are occupied by Fe1, Fe2, and Zn ions, respectively, forming a trinuclear metal center liganded by seven histidines, one aspartate, one glutamate, and one hydroxide with two Fe ions bridged by the hydroxide. In the complexes, the sulfate or phosphate ion is coordinated to three metal ions, resulting in octahedral, trigonal bipyramidal, and tetrahedral geometries around the Fe1, Fe2, and Zn ions, respectively. The ligand residues are derived from the four motifs that characterize the PHP family and from two motifs conserved in histidinol phosphate phosphatases. The (betaalpha)7 barrel and the metal cluster are closely related in nature and architecture to the (betaalpha)8 barrel and the mononuclear or dinuclear metal center in the amidohydrolase superfamily, respectively. The coordination behavior of the phosphate ion toward the metal center supports the mechanism in which the bridging hydroxide makes a direct attack on the substrate phosphate tridentately bound to the two Fe ions and Zn ion to hydrolyze the phosphoester bond.
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PMID:Crystal structure of monofunctional histidinol phosphate phosphatase from Thermus thermophilus HB8. 1792 34

The rate of reliable protein function annotation has not kept pace with the rapid advances in genome sequencing technology. This has created a gap between the number of available protein sequences, and an accurate determination of the respective physiological functions. This investigation has attempted to bridge the gap within the confines of members of the polymerase and histidinol phosphatase family of proteins in cog1387 and cog0613, which is related to the amidohydrolase superfamily. The adopted approach relies on using the mechanistic knowledge of a known enzymatic reaction, and discovering functions of closely related homologs using various tools including bioinformatics and rational library screening. The initial enzymatic reaction was that of L-histidinol phosphate phosphatase. Extensive structural, biochemical, and bioinformatic analysis of enzymes capable of hydrolyzing L-histidinol phosphate provided useful insights in predicting substrates and mechanistic studies of related enzymes. This led to the discovery of unprecedented catalytic functions such as a cyclic phosphate dihydrolase that specifically hydrolyzed a cyclic phosphodiester to inorganic phosphate and a vicinal diol; a phosphoesterase that hydrolyzes the 3'-phosphate of 3',5'-adenosine bisphosphate and similar nucleotides; and the first reported 5'-3' exonuclease for 5'-phosphorylated oligonucleotides from Escherichia coli and related organisms. This work provides a template for developing sequence-structure-function correlations within a family of enzymes that helps expedite new enzyme function discovery and more accurate annotations in protein databases.
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PMID:Structure, Mechanism, and Substrate Profiles of the Trinuclear Metallophosphatases from the Amidohydrolase Superfamily. 3014 58