L.L. Fofanof: 140th anniversary of his birth. Contribution to science

The article is dedicated to Professor L.L. Fofanof’s scientific activity. He headed the faculty therapeutic clinic of Kazan Imperial University in 1915-1920. Being a student L.L. Fofanov was interested in pathological anatomy and physiology. His dissertation «To physiology of n. depressoris» was dedicated to studying the vasomotor center. During his visit in Germany he worked a lot. In Charite together with Professor His he studied gout and its treatment with Radium emanation. In Halle clinic under Professor Schmidt’s supervision he studied assimilation of starch in normal and pathological digestion. L.L. Fofanov also made a contribution to tuberculosis treatment: with professor V.F. Orlovskiy he studied treatment of tuberculosis with simulated pneumothorax. In his research professor L.L. Fofanov paid great attention to the issues of pathogenesis and pathogenetic substantiation of the clinical manifestation and treatment. During the World War I and Civil War he fought against typhus epidemies: he saw patients, gave lectures, studied the features of myocardial involvement. He died in 1920 from typhus

Synthesis of 5-Hydroxyectoine from Ectoine: Crystal Structure of the Non-Heme Iron(II) and 2-Oxoglutarate-Dependent Dioxygenase EctD

As a response to high osmolality, many microorganisms synthesize various types of compatible solutes. These organic osmolytes aid in offsetting the detrimental effects of low water activity on cell physiology. One of these compatible solutes is ectoine. A sub-group of the ectoine producer's enzymatically convert this tetrahydropyrimidine into a hydroxylated derivative, 5-hydroxyectoine. This compound also functions as an effective osmostress protectant and compatible solute but it possesses properties that differ in several aspects from those of ectoine. The enzyme responsible for ectoine hydroxylation (EctD) is a member of the non-heme iron(II)-containing and 2-oxoglutarate-dependent dioxygenases (EC 1.14.11). These enzymes couple the decarboxylation of 2-oxoglutarate with the formation of a high-energy ferryl-oxo intermediate to catalyze the oxidation of the bound organic substrate. We report here the crystal structure of the ectoine hydroxylase EctD from the moderate halophile Virgibacillus salexigens in complex with Fe3+ at a resolution of 1.85 Å. Like other non-heme iron(II) and 2-oxoglutarate dependent dioxygenases, the core of the EctD structure consists of a double-stranded β-helix forming the main portion of the active-site of the enzyme. The positioning of the iron ligand in the active-site of EctD is mediated by an evolutionarily conserved 2-His-1-carboxylate iron-binding motif. The side chains of the three residues forming this iron-binding site protrude into a deep cavity in the EctD structure that also harbours the 2-oxoglutarate co-substrate-binding site. Database searches revealed a widespread occurrence of EctD-type proteins in members of the Bacteria but only in a single representative of the Archaea, the marine crenarchaeon Nitrosopumilus maritimus. The EctD crystal structure reported here can serve as a template to guide further biochemical and structural studies of this biotechnologically interesting enzyme family