scholarly journals Metallochaperones and metalloregulation in bacteria

2017 ◽  
Vol 61 (2) ◽  
pp. 177-200 ◽  
Author(s):  
Daiana A. Capdevila ◽  
Katherine A. Edmonds ◽  
David P. Giedroc
Keyword(s):  
Transition Metal ◽  
Active Site ◽  
Adaptive Response ◽  
Bacterial Infections ◽  
Transcriptional Regulators ◽  
Essential Metals ◽  
Metalloregulatory Proteins ◽  
Metal Cofactors ◽  
Structural Mechanisms ◽  
Metal Sensing

Bacterial transition metal homoeostasis or simply ‘metallostasis’ describes the process by which cells control the intracellular availability of functionally required metal cofactors, from manganese (Mn) to zinc (Zn), avoiding both metal deprivation and toxicity. Metallostasis is an emerging aspect of the vertebrate host–pathogen interface that is defined by a ‘tug-of-war’ for biologically essential metals and provides the motivation for much recent work in this area. The host employs a number of strategies to starve the microbial pathogen of essential metals, while for others attempts to limit bacterial infections by leveraging highly competitive metals. Bacteria must be capable of adapting to these efforts to remodel the transition metal landscape and employ highly specialized metal sensing transcriptional regulators, termed metalloregulatory proteins,and metallochaperones, that allocate metals to specific destinations, to mediate this adaptive response. In this essay, we discuss recent progress in our understanding of the structural mechanisms and metal specificity of this adaptive response, focusing on energy-requiring metallochaperones that play roles in the metallocofactor active site assembly in metalloenzymes and metallosensors, which govern the systems-level response to metal limitation and intoxication.

Metalloregulatory proteins and nitric oxide signalling in bacteria

2008 ◽  
Vol 36 (6) ◽  
pp. 1160-1164 ◽  
Author(s):  
Stephen Spiro
Keyword(s):  
Nitric Oxide ◽  
Transition Metal ◽  
Present Article ◽  
Binding Sites ◽  
Bacterial Gene ◽  
Recent Developments ◽  
Metalloregulatory Proteins ◽  
Metal Cofactors ◽  
Small Ligands

Bacterial gene regulators containing transition metal cofactors that function as binding sites for small ligands were first described in the 1990s. Since then, numerous metal-containing regulators have been discovered, and our knowledge of the diversity of proteins, their cofactors and the signals that they sense has greatly increased. The present article reviews recent developments, with a particular focus on bacterial sensors of nitric oxide.

Active site engineering of atomically dispersed transition metal-heteroatom-carbon catalysts for oxygen reduction

2021 ◽  
Author(s):  
Jiawei Zhu ◽  
Shichun Mu
Keyword(s):  
Transition Metal ◽  
Oxygen Reduction ◽  
Active Site ◽  
Catalytic Reactions ◽  
Single Atom ◽  
Carbon Catalysts

Owing to the advantage of atomic utilization, the single-atom catalyst has attracted much attention and been employed in multifarious catalytic reactions. Their definite site configuration is favorable for exploring the...

Two-Dimensional Transition Metal Borides as High Activity and Selectivity Catalysts for Ammonia Synthesis

Nanoscale ◽  
2021 ◽  
Author(s):  
Haona Zhang ◽  
Shuhua Wang ◽  
Hao Wang ◽  
Baibiao Huang ◽  
Shuping Dong ◽  
...  
Keyword(s):  
Transition Metal ◽  
Specific Surface ◽  
High Activity ◽  
Surface Area ◽  
Active Site ◽  
Ammonia Synthesis ◽  
Two Dimensional ◽  
Large Specific Surface Area ◽  
Site Density ◽  
Metal Borides

In comparison to defect/doping induced activity in materials, transition metal borides with exposed metal atom, large specific surface area and high active site density show advantages as durable and efficient...

New cobalt(ii) coordination designs and the influence of varying chelate characters, ligand charges and incorporated group I metal ions on enzyme-like oxidative coupling activity

2020 ◽  
Vol 44 (35) ◽  
pp. 14849-14858
Author(s):  
Hammed Olawale Oloyede ◽  
Joseph Anthony Orighomisan Woods ◽  
Helmar Görls ◽  
Winfried Plass ◽  
Abiodun Omokehinde Eseola
Keyword(s):  
Transition Metal ◽  
Metal Ions ◽  
Active Site ◽  
Oxidative Coupling ◽  
Reaction Conditions ◽  
Group I ◽  
Mediated Catalysis

In transition-metal-mediated catalysis, design of new, well defined coordination architectures and subjecting them to catalysis testing under the same reaction conditions is a necessity tool for improved understanding of desirable active site geometries and characteristics.

Endonuclease Active Site Plasticity Allows DNA Cleavage with Diverse Alkaline Earth and Transition Metal Ions

2011 ◽  
Vol 6 (9) ◽  
pp. 934-942 ◽  
Author(s):  
Kommireddy Vasu ◽  
Matheshwaran Saravanan ◽  
Valakunja Nagaraja
Keyword(s):  
Transition Metal ◽  
Metal Ions ◽  
Active Site ◽  
Dna Cleavage ◽  
Alkaline Earth ◽  
Transition Metal Ions

scholarly journals Caveat mutator: alanine substitutions for conserved amino acids in RNA ligase elicit unexpected rearrangements of the active site for lysine adenylylation

2020 ◽  
Vol 48 (10) ◽  
pp. 5603-5615
Author(s):  
Mihaela-Carmen Unciuleac ◽  
Yehuda Goldgur ◽  
Stewart Shuman
Keyword(s):  
Crystal Structure ◽  
Active Site ◽  
Active Sites ◽  
Enzyme Structure ◽  
Rna Ligase ◽  
Alanine Scan ◽  
Unexpected Findings ◽  
Metal Cofactors ◽  
Conserved Amino Acids ◽  
Naegleria Gruberi

Abstract Naegleria gruberi RNA ligase (NgrRnl) exemplifies the Rnl5 family of adenosine triphosphate (ATP)-dependent polynucleotide ligases that seal 3′-OH RNA strands in the context of 3′-OH/5′-PO4 nicked duplexes. Like all classic ligases, NgrRnl forms a covalent lysyl–AMP intermediate. A two-metal mechanism of lysine adenylylation was established via a crystal structure of the NgrRnl•ATP•(Mn2+)2 Michaelis complex. Here we conducted an alanine scan of active site constituents that engage the ATP phosphates and the metal cofactors. We then determined crystal structures of ligase-defective NgrRnl-Ala mutants in complexes with ATP/Mn2+. The unexpected findings were that mutations K170A, E227A, K326A and R149A (none of which impacted overall enzyme structure) triggered adverse secondary changes in the active site entailing dislocations of the ATP phosphates, altered contacts to ATP, and variations in the numbers and positions of the metal ions that perverted the active sites into off-pathway states incompatible with lysine adenylylation. Each alanine mutation elicited a distinctive off-pathway distortion of the ligase active site. Our results illuminate a surprising plasticity of the ligase active site in its interactions with ATP and metals. More broadly, they underscore a valuable caveat when interpreting mutational data in the course of enzyme structure-function studies.

Roles of the active site residues and metal cofactors in noncanonical base-pairing during catalysis by human DNA polymerase iota

DNA Repair ◽  
2014 ◽  
Vol 22 ◽  
pp. 67-76 ◽  
Author(s):  
Alena V. Makarova ◽  
Artem Ignatov ◽  
Nataliya Miropolskaya ◽  
Andrey Kulbachinskiy
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Active Site Residues ◽  
Base Pairing ◽  
Dna Polymerase Iota ◽  
Human Dna ◽  
Metal Cofactors

scholarly journals Calpain 3 Is Activated through Autolysis within the Active Site and Lyses Sarcomeric and Sarcolemmal Components

2003 ◽  
Vol 23 (24) ◽  
pp. 9127-9135 ◽  
Author(s):  
Mathieu Taveau ◽  
Nathalie Bourg ◽  
Guillaume Sillon ◽  
Carinne Roudaut ◽  
Marc Bartoli ◽  
...  
Keyword(s):  
Active Site ◽  
Adaptive Response ◽  
Focal Adhesions ◽  
Muscle Cells ◽  
Cysteine Proteases ◽  
Activation Mechanism ◽  
Calpain 3 ◽  
Endogenous Proteins ◽  
Lines Of Evidence

ABSTRACT Calpain 3 (Capn3) is known as the skeletal muscle-specific member of the calpains, a family of intracellular nonlysosomal cysteine proteases. This enigmatic protease has many unique features among the calpain family and, importantly, mutations in Capn3 have been shown to be responsible for limb girdle muscular dystrophy type 2A. Here we demonstrate that the Capn3 activation mechanism is similar to the universal activation of caspases and corresponds to an autolysis within the active site of the protease. We undertook a search for substrates in immature muscle cells, as several lines of evidence suggest that Capn3 is mostly in an inactive state in muscle and needs a signal to be activated. In this model, Capn3 proteolytic activity leads to disruption of the actin cytoskeleton and disorganization of focal adhesions through cleavage of several endogenous proteins. In addition, we show that titin, a previously identified Capn3 partner, and filamin C are further substrates of Capn3. Finally, we report that Capn3 colocalizes in vivo with its substrates at various sites along cytoskeletal structures. We propose that Capn3-mediated cleavage produces an adaptive response of muscle cells to external and/or internal stimuli, establishing Capn3 as a muscle cytoskeleton regulator.

scholarly journals Restriction of bacterial growth by inhibition of polyamine biosynthesis by using monofluoromethylornithine, difluoromethylarginine and dicyclohexylammonium sulphate

1982 ◽  
Vol 208 (2) ◽  
pp. 435-441 ◽  
Author(s):  
A J Bitonti ◽  
P P McCann ◽  
A Sjoerdsma
Keyword(s):  
Escherichia Coli ◽  
Ornithine Decarboxylase ◽  
Bacterial Growth ◽  
Active Site ◽  
Bacterial Infections ◽  
Polyamine Biosynthesis ◽  
E Coli ◽  
Subsequent Investigation ◽  
Generation Times ◽  
Viable Approach

Bacterial growth was measurably slowed by a combination of drugs which inhibit polyamine-biosynthetic enzymes. Addition of DL-alpha-monofluoromethylornithine, which was shown to inactivate irreversibly ornithine decarboxylase extracted from Escherichia coli (Ki = 0.36 mM) and Pseudomonas aeruginosa (Ki = 0.30 mM), DL-alpha-difluoromethylarginine and dicyclohexylammonium sulphate to cultures of E. coli or P. aeruginosa resulted in a 40 and 70% increase in generation times (decreased growth rates) respectively, which was completely reversed by the addition of 0.1 mM-putrescine plus 0.1 mM-spermidine to the medium. Decreased intracellular polyamine concentrations correlated with increased generation times; putrescine concentration was decreased by 70% in E. coli and 80% in P. aeruginosa, while spermidine concentration was decreased by 50% in E. coli and 95% in P. aeruginosa. Subsequent investigation of the inactivation of the ornithine decarboxylase by monofluoromethylornithine indicated that it was active-site directed, as the normal substrate ornithine slowed the rate of inhibition. Specific interference with polyamine biosynthesis may be a viable approach to control of some bacterial infections.

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