1wvq
Structure of conserved hypothetical protein PAE2307 from Pyrobaculum aerophilum
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPhosphorylation of both small molecules and proteins plays a central role in many biological processes. In proteins, phosphorylation most commonly targets the oxygen atoms of Ser, Thr, and Tyr. In contrast, stably phosphorylated His residues are rarely found, due to the lability of the N-P bond, and histidine phosphorylation features most often in transient processes. Here we present the crystal structure of a protein of previously unknown function, which proves to contain a stably phosphorylated histidine residue. The protein is the product of open reading frame PAE2307, from the hyperthermophilic archaeon Pyrobaculum aerophilum, and is representative of a highly conserved protein family found in archaea and bacteria. The crystal structure of PAE2307, solved at 1.45-A resolution (R = 0.208, R(free) = 0.227), forms a remarkably tightly associated hexamer. The phosphorylated histidine at the proposed active site, pHis85, occupies a cavity that is at the interface between two subunits and contains a number of fully conserved residues. Stable phosphorylation is attributed to favorable hydrogen bonding of the phosphoryl group and a salt bridge with pHis85 that provides electronic stabilization. In silico modeling suggested that the protein may function as an adenosine kinase, a conclusion that is supported by in vitro assays of adenosine binding, using fluorescence spectroscopy, and crystallographic visualization of an adenosine complex of PAE2307 at 2.25-A resolution. The structure of an ancient conserved domain establishes a structural basis for stable histidine phosphorylation and identifies a new family of adenosine-specific kinases.,Lott JS, Paget B, Johnston JM, Delbaere LT, Sigrell-Simon JA, Banfield MJ, Baker EN J Biol Chem. 2006 Aug 4;281(31):22131-41. Epub 2006 May 30. PMID:16737961[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
