1.
Evolution of Macromolecular Docking Techniques: The Case Study of Nickel and Iron Metabolism in Pathogenic Bacteria.
Musiani, F, Ciurli, S
Molecules (Basel, Switzerland). 2015;(8):14265-92
Abstract
The interaction between macromolecules is a fundamental aspect of most biological processes. The computational techniques used to study protein-protein and protein-nucleic acid interactions have evolved in the last few years because of the development of new algorithms that allow the a priori incorporation, in the docking process, of experimentally derived information, together with the possibility of accounting for the flexibility of the interacting molecules. Here we review the results and the evolution of the techniques used to study the interaction between metallo-proteins and DNA operators, all involved in the nickel and iron metabolism of pathogenic bacteria, focusing in particular on Helicobacter pylori (Hp). In the first part of the article we discuss the methods used to calculate the structure of complexes of proteins involved in the activation of the nickel-dependent enzyme urease. In the second part of the article, we concentrate on two applications of protein-DNA docking conducted on the transcription factors HpFur (ferric uptake regulator) and HpNikR (nickel regulator). In both cases we discuss the technical expedients used to take into account the conformational variability of the multi-domain proteins involved in the calculations.
2.
Common themes and unique proteins for the uptake and trafficking of nickel, a metal essential for the virulence of Helicobacter pylori.
de Reuse, H, Vinella, D, Cavazza, C
Frontiers in cellular and infection microbiology. 2013;:94
Abstract
Nickel is a virulence determinant for the human gastric pathogen Helicobacter pylori. Indeed, H. pylori possesses two nickel-enzymes that are essential for in vivo colonization, [NiFe] hydrogenase and urease, an abundant virulence factor that contains 24 nickel ions per active complex. Because of these two enzymes, survival of H. pylori relies on an important supply of nickel, implying a tight control of its distribution and storage. In this review, we will present the pathways of activation of the nickel enzymes as well as original mechanisms found in H. pylori for the uptake, trafficking and distribution of nickel between the two enzymes. These include (i) an outer-membrane nickel uptake system, the FrpB4 TonB-dependent transporter, (ii) overlapping protein complexes and interaction networks involved in nickel trafficking and distribution between urease and hydrogenase and, (iii) Helicobacter specific nickel-binding proteins that are involved in nickel storage and can play the role of metallo-chaperones. Finally, we will discuss the implication of the nickel trafficking partners in virulence and propose them as novel therapeutic targets for treatments against H. pylori infection.
3.
Unrecognized risks of nickel-related respiratory cancer among Canadian electrolysis workers.
Grimsrud, TK, Andersen, A
Scandinavian journal of work, environment & health. 2012;(6):503-15
Abstract
OBJECTIVES Nickel compounds, inclusive of water-soluble salts, have been classified as human carcinogens by the International Agency for Research on Cancer (IARC). Nickel producers have disputed the classification of soluble nickel compounds for three decades with reference to an alleged absence of excess respiratory cancer among Canadian nickel-exposed electrolysis workers. We evaluated historical data from two electrolytic refineries in Ontario, both included in prominent Canadian reports on occupational nickel-related cancer. METHODS For Port Colborne nickel refinery (PCNR) and Copper Cliff copper refinery (CCCR), we identified process descriptions, exposure estimates, and original reports on cancer mortality using reference lists, libraries, and state archives. The documents were written or published between 1930 and 1992. RESULTS For PCNR, a 1977 US National Institute of Occupational Safety and Health criteria document demonstrated an excess nasal cancer risk among electrolysis workers independent of furnace exposure. PCNR studies published after 1980 excluded 26% of long-term refiners who died from respiratory cancer according to earlier reports, and 42% of the workers had unknown vital status at the end of follow-up, biasing the standardized observed-to-expected mortality ratios downwards, most pronounced in recent reports and for workers without pension or company benefits. CCCR reports did not adequately address soluble nickel exposure in the evaluation of an observed occupational lung cancer excess. CONCLUSIONS While acknowledging important contributions to the recognition of nickel carcinogenicity from highly exposed Canadian refiners, we conclude that the claimed absence of nickel-related respiratory cancer among electrolysis workers has resulted from an arbitrary overemphasis of biased and inconclusive findings.
4.
Nickel uptake and utilization by microorganisms.
Mulrooney, SB, Hausinger, RP
FEMS microbiology reviews. 2003;(2-3):239-61
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Abstract
Nickel is an essential nutrient for selected microorganisms where it participates in a variety of cellular processes. Many microbes are capable of sensing cellular nickel ion concentrations and taking up this nutrient via nickel-specific permeases or ATP-binding cassette-type transport systems. The metal ion is specifically incorporated into nickel-dependent enzymes, often via complex assembly processes requiring accessory proteins and additional non-protein components, in some cases accompanied by nucleotide triphosphate hydrolysis. To date, nine nickel-containing enzymes are known: urease, NiFe-hydrogenase, carbon monoxide dehydrogenase, acetyl-CoA decarbonylase/synthase, methyl coenzyme M reductase, certain superoxide dismutases, some glyoxylases, aci-reductone dioxygenase, and methylenediurease. Seven of these enzymes have been structurally characterized, revealing distinct metallocenter environments in each case.