American Corner Lectures | Robert P. Hausinger

 

Urease and Nickel in Biology

Robert P. Hausinger

Michigan State University

Dia 14 maio | Auditório | 14:30

Abstract

Urease, the first enzyme to be crystallized and the first shown to possess nickel, catalyzes a simple reaction, but it requires a remarkably complex biosynthesis machinery. Formation of the dinuclear nickel metallocenter with its bridging carbamylated lysyl ligand is dependent on the functions of the metallochaperone UreE, the GTPase UreG, and the protein scaffold UreF/UreD that contains a molecular tunnel through which nickel must pass. Other nickel-containing enzymes include guanidinase, glyoxylase, acireductone dioxygenase, superoxide dismutase, [NiFe] hydrogenase, carbon monoxide dehydrogenase, acetyl-CoA synthase/decarbonylase, hydroxyacid racemase/epimerase, and methyl coenzyme M reductase. The metallocenters in these enzymes encompass mononuclear and dinuclear sites, more complex clusters, and organometallic complexes, where the biosynthetic pathways for several of these enzymes are also complex. In contrast to its essential functions, nickel exhibits toxicity in animals, plants, and microorganisms. Homeostatic control of nickel concentrations involves nickel-dependent transcriptional regulators and nickel transporters. A recent intriguing aspect of the biology of nickel is its use in long-distance (centimeter-long) electron transfer via periplasmic filaments in cable bacteria.

Hausinger, R. P. 2022. Microbial metabolism of nickel. In Microbial Metabolism of Metals and Metalloids, (Ed. Hurst, C. J.), Springer. pp. 415-502. doi: 10.1007/978-3-030-97185-4_14.

Short Bio

My research interests center on enzyme mechanisms. The most significant investigations in my laboratory have focused on the characterization of pathways for metalloenzyme synthesis and the elucidation of catalytic mechanisms for metal-containing enzymes, with particular emphasis on the nickel-containing enzymes lactate racemase and urease along with iron- and 2-oxoglutarate-dependent oxygenases that include representatives involved in DNA repair, sulfonate metabolism, and ethylene biosynthesis. Most of these projects involve bacterial metabolism and physiology, but we have also worked on systems from fungal, protozoal, and mammalian cells.