The structure-based reaction mechanism of urease, a nickel dependent enzyme: tale of a long debate
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MINI REVIEW
The structure‑based reaction mechanism of urease, a nickel dependent enzyme: tale of a long debate Luca Mazzei1 · Francesco Musiani1 · Stefano Ciurli1 Received: 30 May 2020 / Accepted: 29 June 2020 © The Author(s) 2020
Abstract This review is an attempt to retrace the chronicle that starts from the discovery of the role of nickel as the essential metal ion in urease for the enzymatic catalysis of urea, a key step in the biogeochemical cycle of nitrogen on Earth, to the most recent progress in understanding the chemistry of this historical enzyme. Data and facts are presented through the magnifying lenses of the authors, using their best judgment to filter and elaborate on the many facets of the research carried out on this metalloenzyme over the years. The tale is divided in chapters that discuss and describe the results obtained in the subsequent leaps in the knowledge that led from the discovery of a biological role for Ni to the most recent advancements in the comprehension of the relationship between the structure and function of urease. This review is intended not only to focus on the bioinorganic chemistry of this beautiful metal-based catalysis, but also, and maybe primarily, to evoke inspiration and motivation to further explore the realm of bio-based coordination chemistry. Keywords Nickel · Urease · Catalytic mechanism · Crystal structure · Sporosarcina pasteurii · Klebsiella aerogenes · Helicobacter pylori
Introduction Urease (urea amidohydrolase E.C. 3.5.1.5) is a nickeldependent enzyme found in a large variety of organisms, including plants, algae, fungi, and several prokaryotes [1, 2]. It is critically involved in the mineralization step of the global nitrogen cycle, being able to catalyze the rapid hydrolytic decomposition of urea to produce ammonia and carbamate, the latter eventually decomposing spontaneously into a second molecule of ammonia and bicarbonate (Scheme 1) [3–6]. This catalytic activity triggers a rapid overall pH increase of the milieu (Scheme 2) that has negative effects both on human health [7] and agriculture [8]. This alkalization effect is utilized by numerous human pathogenic microorganisms that exploit urease as a virulence factor to infect and colonize the host [7, 9, 10]. The priority pathogen list indicated by the World Health Organization for the research and development of new antibiotics * Stefano Ciurli [email protected] 1
Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale G. Fanin 40, 40127 Bologna, Italy
[11] includes urease-dependent antibiotic-resistant bacteria, several of which are involved in bacterial infections of the respiratory apparatus, and it is remarkable that half of patients who died of the recent COVID-19 epidemics in Wuhan (China) became co-infected with bacteria in the lungs and also required antibiotics [12]. In particular, Helicobacter pylori infection, affecting large portions of the entire human population, causes a series of gastrointestinal diseases, includ
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