scholarly journals Methanobactin and the Link between Copper and Bacterial Methane Oxidation

2016 ◽  
Vol 80 (2) ◽  
pp. 387-409 ◽  
Author(s):  
Alan A. DiSpirito ◽  
Jeremy D. Semrau ◽  
J. Colin Murrell ◽  
Warren H. Gallagher ◽  
Christopher Dennison ◽  
...  
Keyword(s):  
Transition Metals ◽  
Posttranslational Modifications ◽  
Metal Binding ◽  
Copper Ions ◽  
Peptide Sequence ◽  
Leader Peptide ◽  
Copper Binding ◽  
Methane Oxidizing Bacteria ◽  
Peptide Precursor ◽  
Potential Applications

SUMMARYMethanobactins (mbs) are low-molecular-mass (<1,200 Da) copper-binding peptides, or chalkophores, produced by many methane-oxidizing bacteria (methanotrophs). These molecules exhibit similarities to certain iron-binding siderophores but are expressed and secreted in response to copper limitation. Structurally, mbs are characterized by a pair of heterocyclic rings with associated thioamide groups that form the copper coordination site. One of the rings is always an oxazolone and the second ring an oxazolone, an imidazolone, or a pyrazinedione moiety. The mb molecule originates from a peptide precursor that undergoes a series of posttranslational modifications, including (i) ring formation, (ii) cleavage of a leader peptide sequence, and (iii) in some cases, addition of a sulfate group. Functionally, mbs represent the extracellular component of a copper acquisition system. Consistent with this role in copper acquisition, mbs have a high affinity for copper ions. Following binding, mbs rapidly reduce Cu2+to Cu1+. In addition to binding copper, mbs will bind most transition metals and near-transition metals and protect the host methanotroph as well as other bacteria from toxic metals. Several other physiological functions have been assigned to mbs, based primarily on their redox and metal-binding properties. In this review, we examine the current state of knowledge of this novel type of metal-binding peptide. We also explore its potential applications, how mbs may alter the bioavailability of multiple metals, and the many roles mbs may play in the physiology of methanotrophs.

scholarly journals Copper Binding Features of Tropomyosin-Receptor-Kinase-A Fragment: Clue for Neurotrophic Factors and Metals Link

2018 ◽  
Vol 19 (8) ◽  
pp. 2374 ◽  
Author(s):  
Antonio Magrì ◽  
Diego La Mendola
Keyword(s):  
Metal Binding ◽  
Copper Ions ◽  
Spectroscopic Studies ◽  
Copper Binding ◽  
Receptor Kinase ◽  
Amide Nitrogen ◽  
Trka Receptor ◽  
Peptide Backbone ◽  
Specific Domain ◽  
Backbone Amide

The nerve growth factor (NGF) is a neurotrophin essential for the development and maintenance of neurons, whose activity is influenced by copper ions. The NGF protein exerts its action by binding to its specific receptor, TrkA. In this study, a specific domain of the TrkA receptor, region 58–64, was synthesized and its copper(II) complexes characterized by means of potentiometric and spectroscopic studies. The two vicinal histidine residues provide excellent metal anchoring sites and, at physiological pH, a complex with the involvement of the peptide backbone amide nitrogen is the predominant species. The TrkA peptide is competitive for metal binding with analogous peptides due to the N-terminal domain of NGF. These data provide cues for future exploration of the effect of metal ions on the activity of the NGF and its specific cellular receptor.

scholarly journals Biosynthesis and Transport of the Lantibiotic Mutacin 1140 Produced by Streptococcus mutans

2015 ◽  
Vol 197 (7) ◽  
pp. 1173-1184 ◽  
Author(s):  
Jerome Escano ◽  
Byron Stauffer ◽  
Jacob Brennan ◽  
Monica Bullock ◽  
Leif Smith
Keyword(s):  
Streptococcus Mutans ◽  
Posttranslational Modifications ◽  
Cleavage Site ◽  
Peptide Sequence ◽  
Leader Peptide ◽  
Peptide Antibiotics ◽  
The Core ◽  
Core Peptide ◽  
Mutacin 1140 ◽  
Secondary Cleavage

ABSTRACTLantibiotics are ribosomally synthesized peptide antibiotics composed of an N-terminal leader peptide that is cleaved to yield the active antibacterial peptide. Significant advancements in molecular tools that promote the study of lantibiotic biosynthesis can be used inStreptococcus mutans. Herein, we further our understanding of leader peptide sequence and core peptide structural requirements for the biosynthesis and transport of the lantibiotic mutacin 1140. Our study on mutacin 1140 biosynthesis shows a dedicated secondary cleavage site within the leader peptide and the dependency of transport on core peptide posttranslational modifications (PTMs). The secondary cleavage site on the leader peptide is found at the −9 position, and secondary cleavage occurs before the core peptide is transported out of the cell. The coordinated cleavage at the −9 position was absent in alanTdeletion strain, suggesting that the core peptide interaction with the LanT transporter enables uniform cleavage at the −9 position. Following transport, the LanP protease was found to be tolerant to a wide variety of amino acid substitutions at the primary leader peptide cleavage site, with the exception of arginine at the −1 position. Several leader and core peptide mutations produced core peptide variants that had intermediate stages of PTM enzyme modifications, supporting the concept that PTM enzyme modifications, secondary cleavage, and transport are occurring in a highly coordinated fashion.IMPORTANCEMutacin 1140 belongs to the class I lantibiotic family of ribosomally synthesized and posttranslationally modified peptides (RiPPs). The biosynthesis of mutacin 1140 is a highly efficient process which does not lead to a discernible level of production of partially modified core peptide variants. The products isolated from an extensive mutagenesis study on the leader and core peptides of mutacin 1140 show that the posttranslational modifications (PTMs) on the core peptide occur under a highly coordinated dynamic process. PTMs are dictated by the distance of the core peptide modifiable residues from PTM enzyme active sites. The formation of lanthionine rings aids in the formation of successive PTMs, as was observed in a peptide variant lacking a C-terminal decarboxylation.

scholarly journals The bacterial copper resistance protein CopG contains a cysteine-bridged tetranuclear copper cluster

2020 ◽  
Vol 295 (32) ◽  
pp. 11364-11376 ◽  
Author(s):  
Andrew C. Hausrath ◽  
Nicholas A. Ramirez ◽  
Alan T. Ly ◽  
Megan M. McEvoy
Keyword(s):  
Metal Binding ◽  
Biochemical Characterization ◽  
Copper Ions ◽  
Three Dimensional ◽  
Copper Resistance ◽  
Dimensional Structure ◽  
Copper Binding ◽  
Uncharacterized Protein ◽  
X Ray Crystallography ◽  
Biochemical Analyses

CopG is an uncharacterized protein ubiquitous in Gram-negative bacteria whose gene frequently occurs in clusters of copper resistance genes and can be recognized by the presence of a conserved CxCC motif. To investigate its contribution to copper resistance, here we undertook a structural and biochemical characterization of the CopG protein from Pseudomonas aeruginosa. Results from biochemical analyses of CopG purified under aerobic conditions indicate that it is a green copper-binding protein that displays absorbance maxima near 411, 581, and 721 nm and is monomeric in solution. Determination of the three-dimensional structure by X-ray crystallography revealed that CopG consists of a thioredoxin domain with a C-terminal extension that contributes to metal binding. We noted that adjacent to the CxCC motif is a cluster of four copper ions bridged by cysteine sulfur atoms. Structures of CopG in two oxidation states support the assignment of this protein as an oxidoreductase. On the basis of these structural and spectroscopic findings and also genetic evidence, we propose that CopG has a role in interconverting Cu(I) and Cu(II) to minimize toxic effects and facilitate export by the Cus RND transporter efflux system.

scholarly journals Hyaluronate/black phosphorus complexes as a copper chelating agent for Wilson disease treatment

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Seong-Jong Kim ◽  
Hye Hyeon Han ◽  
Sei Kwang Hahn
Keyword(s):  
Targeted Delivery ◽  
Wilson Disease ◽  
Copper Ions ◽  
Binding Capacity ◽  
Genetic Disorder ◽  
Chelating Agent ◽  
Black Phosphorus ◽  
The Body ◽  
Copper Binding

Abstract Background Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD. Methods We developed hyaluronate-diaminohexane/black phosphorus (HA-DAH/BP) complexes for capturing copper ions accumulated in the liver for the treatment of WD. Results HA-DAH/BP complexes showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-DAH/BP complexes to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-DAH/BP complexes. Conclusion HA-DAH/BP complexes would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.

Copper chaperone Atox1 interacts with the metal-binding domain of Wilson's disease protein in cisplatin detoxification

2013 ◽  
Vol 454 (1) ◽  
pp. 147-156 ◽  
Author(s):  
Nataliya V. Dolgova ◽  
Sergiy Nokhrin ◽  
Corey H. Yu ◽  
Graham N. George ◽  
Oleg Y. Dmitriev
Keyword(s):  
Metal Binding ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Binding Domain ◽  
Binding Motif ◽  
Copper Chaperone ◽  
Copper Binding ◽  
Copper Transporters ◽  
Metal Binding Domain ◽  
Disease Protein

Human copper transporters ATP7B (Wilson's disease protein) and ATP7A (Menkes' disease protein) have been implicated in tumour resistance to cisplatin, a widely used anticancer drug. Cisplatin binds to the copper-binding sites in the N-terminal domain of ATP7B, and this binding may be an essential step of cisplatin detoxification involving copper ATPases. In the present study, we demonstrate that cisplatin and a related platinum drug carboplatin produce the same adduct following reaction with MBD2 [metal-binding domain (repeat) 2], where platinum is bound to the side chains of the cysteine residues in the CxxC copper-binding motif. This suggests the same mechanism for detoxification of both drugs by ATP7B. Platinum can also be transferred to MBD2 from copper chaperone Atox1, which was shown previously to bind cisplatin. Binding of the free cisplatin and reaction with the cisplatin-loaded Atox1 produce the same protein-bound platinum intermediate. Transfer of platinum along the copper-transport pathways in the cell may serve as a mechanism of drug delivery to its target in the cell nucleus, and explain tumour-cell resistance to cisplatin associated with the overexpression of copper transporters ATP7B and ATP7A.

Development of Multilayered Chlorogenate-Peptide Based Biocomposite Scaffolds for Potential Applications in Ligament Tissue Engineering - An In Vitro Study

2017 ◽  
Vol 34 ◽  
pp. 37-56 ◽  
Author(s):  
Harrison T. Pajovich ◽  
Alexandra M. Brown ◽  
Andrew M. Smith ◽  
Sara K. Hurley ◽  
Jessica R. Dorilio ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Type I Collagen ◽  
Phase Changes ◽  
Peptide Sequence ◽  
Proteoglycan Synthesis ◽  
Type I ◽  
Average Roughness ◽  
Potential Applications ◽  
Self Assembled

In this work, for the first time, chlorogenic acid, a natural phytochemical, was conjugated to a lactoferrin derived antimicrobial peptide sequence RRWQWRMKKLG to develop a self-assembled template. To mimic the components of extracellular matrix, we then incorporated Type I Collagen, followed by a sequence of aggrecan peptide (ATEGQVRVNSIYQDKVSL) onto the self-assembled templates for potential applications in ligament tissue regeneration. Mechanical properties and surface roughness were studied and the scaffolds displayed a Young’s Modulus of 169 MP and an average roughness of 72 nm respectively. Thermal phase changes were studied by DSC analysis. Results showed short endothermic peaks due to water loss and an exothermic peak due to crystallization of the scaffold caused by rearrangement of the components. Biodegradability studies indicated a percent weight loss of 27.5 % over a period of 37 days. Furthermore, the scaffolds were found to adhere to fibroblasts, the main cellular component of ligament tissue. The scaffolds promoted cell proliferation and displayed actin stress fibers indicative of cell motility and attachment. Collagen and proteoglycan synthesis were also promoted, demonstrating increased expression and deposition of collagen and proteoglycans. Additionally, the scaffolds exhibited antimicrobial activity against Staphylococcus epidermis bacteria, which is beneficial for minimizing biofilm formation if potentially used as implants. Thus, we have developed a novel biocomposite that may open new avenues to enhance ligament tissue regeneration.

scholarly journals Metal-binding mechanism of Cox17, a copper chaperone for cytochrome c oxidase

2004 ◽  
Vol 382 (1) ◽  
pp. 307-314 ◽  
Author(s):  
Peep PALUMAA ◽  
Liina KANGUR ◽  
Anastassia VORONOVA ◽  
Rannar SILLARD
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Metal Binding ◽  
Copper Ions ◽  
Copper Chaperone ◽  
Copper Chaperones ◽  
Rate Limiting Step ◽  
Charge State Distributions ◽  
Rate Limiting ◽  
Partner Proteins

Cox17, a copper chaperone for cytochrome c oxidase, is an essential and highly conserved protein. The structure and mechanism of functioning of Cox17 are unknown, and even its metalbinding stoichiometry is elusive. In the present study, we demonstrate, using electrospray ionization–MS, that porcine Cox17 binds co-operatively four Cu+ ions. Cu4Cox17 is stable at pH values above 3 and fluorescence spectra indicate the presence of a solvent-shielded multinuclear Cu(I) cluster. Combining our results with earlier EXAFS results on yeast CuCox17, we suggest that Cu4Cox17 contains a Cu4S6-type cluster. At supramillimolar concentrations, dithiothreitol extracts metals from Cu4Cox17, and an apparent copper dissociation constant KCu=13 fM was calculated from these results. Charge-state distributions of different Cox17 forms suggest that binding of the first Cu+ ion to Cox17 causes a conformational change from an open to a compact state, which may be the rate-limiting step in the formation of Cu4Cox17. Cox17 binds non-co-operatively two Zn2+ ions, but does not bind Ag+ ions, which highlights its extremely high metal-binding specificity. We further demonstrate that porcine Cox17 can also exist in partly oxidized (two disulphide bridges) and fully oxidized (three disulphide bridges) forms. Partly oxidized Cox17 can bind one Cu+ or Zn2+ ion, whereas fully oxidized Cox17 does not bind metals. The metal-binding properties of Cox17 imply that, in contrast with other copper chaperones, Cox17 is designed for the simultaneous transfer of up to four copper ions to partner proteins. Metals can be released from Cox17 by non-oxidative as well as oxidative mechanisms.

scholarly journals Biochemical and molecular characterization of N66 from the shell ofPinctada mazatlanica

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7212
Author(s):  
Crisalejandra Rivera-Perez ◽  
Catalina Magallanes-Dominguez ◽  
Rosa Virginia Dominguez-Beltran ◽  
Josafat Jehu Ojeda-Ramirez de Areyano ◽  
Norma Y. Hernandez-Saavedra
Keyword(s):  
Posttranslational Modifications ◽  
Protein A ◽  
Pearl Oyster ◽  
Peptide Sequence ◽  
Calcium Carbonate Precipitation ◽  
Base Pairs ◽  
Shell Matrix ◽  
Glycosylation Sites ◽  
Shell Matrix Proteins

Mollusk shell mineralization is a tightly controlled process made by shell matrix proteins (SMPs). However, the study of SMPs has been limited to a few model species. In this study, the N66 mRNA of the pearl oysterPinctada mazatlanicawas cloned and functionally characterized. The full sequence of the N66 mRNA comprises 1,766 base pairs, and encodes one N66 protein. A sequence analysis revealed that N66 contained two carbonic anhydrase (CA) domains, a NG domain and several glycosylation sites. The sequence showed similarity to the CA VII but also with its homolog protein nacrein. The native N66 protein was isolated from the shell and identified by mass spectrometry, the peptide sequence matched to the nucleotide sequence obtained. Native N66 is a glycoprotein with a molecular mass of 60–66 kDa which displays CA activity and calcium carbonate precipitation ability in presence of different salts. Also, a recombinant form of N66 was produced inEscherichia coli, and functionally characterized. The recombinant N66 displayed higher CA activity and crystallization capability than the native N66, suggesting that the lack of posttranslational modifications in the recombinant N66 might modulate its activity.

scholarly journals Unevolved De Novo Proteins Have Innate Tendencies to Bind Transition Metals

Life ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 8 ◽  
Author(s):  
Michael S. Wang ◽  
Kenric J. Hoegler ◽  
Michael H. Hecht
Keyword(s):  
Amino Acid ◽  
Transition Metals ◽  
Metal Binding ◽  
Combinatorial Library ◽  
De Novo ◽  
Protein Sequences ◽  
Amino Acid Sequences ◽  
Ancestral Sequences ◽  
Wide Range ◽  
Catalytic Functions

Life as we know it would not exist without the ability of protein sequences to bind metal ions. Transition metals, in particular, play essential roles in a wide range of structural and catalytic functions. The ubiquitous occurrence of metalloproteins in all organisms leads one to ask whether metal binding is an evolved trait that occurred only rarely in ancestral sequences, or alternatively, whether it is an innate property of amino acid sequences, occurring frequently in unevolved sequence space. To address this question, we studied 52 proteins from a combinatorial library of novel sequences designed to fold into 4-helix bundles. Although these sequences were neither designed nor evolved to bind metals, the majority of them have innate tendencies to bind the transition metals copper, cobalt, and zinc with high nanomolar to low-micromolar affinity.

scholarly journals A new approach to biomining: Bioengineering surfaces for metal recovery from aqueous solutions

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jesica Urbina ◽  
Advait Patil ◽  
Kosuke Fujishima ◽  
Ivan G. Paulino-Lima ◽  
Chad Saltikov ◽  
...  
Keyword(s):  
Aqueous Solutions ◽  
Metal Binding ◽  
Raw Materials ◽  
Extraction Methods ◽  
Metal Recovery ◽  
Consumer Electronics ◽  
Metal Extraction ◽  
Copper Binding ◽  
Metal Binding Peptides ◽  
Binding Peptides

Abstract Electronics waste production has been fueled by economic growth and the demand for faster, more efficient consumer electronics. The glass and metals in end-of-life electronics components can be reused or recycled; however, conventional extraction methods rely on energy-intensive processes that are inefficient when applied to recycling e-waste that contains mixed materials and small amounts of metals. To make e-waste recycling economically viable and competitive with obtaining raw materials, recovery methods that lower the cost of metal reclamation and minimize environmental impact need to be developed. Microbial surface adsorption can aid in metal recovery with lower costs and energy requirements than traditional metal-extraction approaches. We introduce a novel method for metal recovery by utilizing metal-binding peptides to functionalize fungal mycelia and enhance metal recovery from aqueous solutions such as those found in bioremediation or biomining processes. Using copper-binding as a proof-of-concept, we compared binding parameters between natural motifs and those derived in silico, and found comparable binding affinity and specificity for Cu. We then combined metal-binding peptides with chitin-binding domains to functionalize a mycelium-based filter to enhance metal recovery from a Cu-rich solution. This finding suggests that engineered peptides could be used to functionalize biological surfaces to recover metals of economic interest and allow for metal recovery from metal-rich effluent with a low environmental footprint, at ambient temperatures, and under circumneutral pH.

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