Browse
Submit Data
Databases
API
Help

Dataset Information

29 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Minimal Heterochiral de Novo Designed 4Fe-4S Binding Peptide Capable of Robust Electron Transfer.

ABSTRACT: Ambidoxin is a designed, minimal dodecapeptide consisting of alternating L and D amino acids that binds a 4Fe-4S cluster through ligand-metal interactions and an extensive network of second-shell hydrogen bonds. The peptide can withstand hundreds of oxidation-reduction cycles at room temperature. Ambidoxin suggests how simple, prebiotic peptides may have achieved robust redox catalysis on the early Earth.

SUBMITTER: Kim JD

PROVIDER: S-EPMC7050467 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Minimal Heterochiral de Novo Designed 4Fe-4S Binding Peptide Capable of Robust Electron Transfer.

Kim J Dongun JD Pike Douglas H DH Tyryshkin Alexei M AM Swapna G V T GVT Raanan Hagai H Montelione Gaetano T GT Nanda Vikas V Falkowski Paul G PG

Journal of the American Chemical Society 20180829 36

Ambidoxin is a designed, minimal dodecapeptide consisting of alternating L and D amino acids that binds a 4Fe-4S cluster through ligand-metal interactions and an extensive network of second-shell hydrogen bonds. The peptide can withstand hundreds of oxidation-reduction cycles at room temperature. Ambidoxin suggests how simple, prebiotic peptides may have achieved robust redox catalysis on the early Earth. ...[more]

PMID: 30141918

Similar Datasets

<i>De Novo</i> Designed Heterochiral Blue Fluorescent Protein.

Project description:Diversification of chain stereochemistry offers a tremendous increase in protein design space. We have designed a minimal fluorescent protein, pregnant with β-(1-azulenyl)-l-alanine in the hydrophobic core of a heterotactic protein scaffold, employing automated design tools such as automated repetitive simulated annealing molecular dynamics and IDeAS. The de novo designed heterochiral protein can be selectively excited at 342 nm, quite distant from the intrinsic fluorophore, and emits in the blue region. The structure and stability of the designed proteins were evaluated by established spectroscopic and calorimetric methods.

| S-EPMC7581079 | biostudies-literature

Structural principles for computational and de novo design of 4Fe-4S metalloproteins.

Project description:Iron-sulfur centers in metalloproteins can access multiple oxidation states over a broad range of potentials, allowing them to participate in a variety of electron transfer reactions and serving as catalysts for high-energy redox processes. The nitrogenase FeMoCO cluster converts di-nitrogen to ammonia in an eight-electron transfer step. The 2(Fe4S4) containing bacterial ferredoxin is an evolutionarily ancient metalloprotein fold and is thought to be a primordial progenitor of extant oxidoreductases. Controlling chemical transformations mediated by iron-sulfur centers such as nitrogen fixation, hydrogen production as well as electron transfer reactions involved in photosynthesis are of tremendous importance for sustainable chemistry and energy production initiatives. As such, there is significant interest in the design of iron-sulfur proteins as minimal models to gain fundamental understanding of complex natural systems and as lead-molecules for industrial and energy applications. Herein, we discuss salient structural characteristics of natural iron-sulfur proteins and how they guide principles for design. Model structures of past designs are analyzed in the context of these principles and potential directions for enhanced designs are presented, and new areas of iron-sulfur protein design are proposed. This article is part of a Special issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, protein networks, edited by Ronald L. Koder and J.L Ross Anderson.

| S-EPMC5389887 | biostudies-literature

Catalysis and Electron Transfer in De Novo Designed Helical Scaffolds.

Project description:The relationship between protein structure and function is one of the greatest puzzles within biochemistry. De novo metalloprotein design is a way to wipe the board clean and determine what is required to build in function from the ground up in an unrelated structure. This Review focuses on protein design efforts to create de novo metalloproteins within alpha-helical scaffolds. Examples of successful designs include those with carbonic anhydrase or nitrite reductase activity by incorporating a ZnHis3 or CuHis3 site, or that recapitulate the spectroscopic properties of unique electron-transfer sites in cupredoxins (CuHis2 Cys) or rubredoxins (FeCys4 ). This work showcases the versatility of alpha helices as scaffolds for metalloprotein design and the progress that is possible through careful rational design. Our studies cover the invariance of carbonic anhydrase activity with different site positions and scaffolds, refinement of our cupredoxin models, and enhancement of nitrite reductase activity up to 1000-fold.

| S-EPMC7035182 | biostudies-literature

Catalysis and Electron Transfer in <i>De Novo</i> Designed Metalloproteins.

Project description:One of the hallmark advances in our understanding of metalloprotein function is showcased in our ability to design new, non-native, catalytically active protein scaffolds. This review highlights progress and milestone achievements in the field of de novo metalloprotein design focused on reports from the past decade with special emphasis on de novo designs couched within common subfields of bioinorganic study: heme binding proteins, monometal- and dimetal-containing catalytic sites, and metal-containing electron transfer sites. Within each subfield, we highlight several of what we have identified as significant and important contributions to either our understanding of that subfield or de novo metalloprotein design as a discipline. These reports are placed in context both historically and scientifically. General suggestions for future directions that we feel will be important to advance our understanding or accelerate discovery are discussed.

| S-EPMC10735231 | biostudies-literature

A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the native enzyme.

Project description:Multielectron redox reactions often require multicofactor metalloenzymes to facilitate coupled electron and proton movement, but it is challenging to design artificial enzymes to catalyze these important reactions, owing to their structural and functional complexity. We report a designed heteronuclear heme-[4Fe-4S] cofactor in cytochrome c peroxidase as a structural and functional model of the enzyme sulfite reductase. The initial model exhibits spectroscopic and ligand-binding properties of the native enzyme, and sulfite reduction activity was improved-through rational tuning of the secondary sphere interactions around the [4Fe-4S] and the substrate-binding sites-to be close to that of the native enzyme. By offering insight into the requirements for a demanding six-electron, seven-proton reaction that has so far eluded synthetic catalysts, this study provides strategies for designing highly functional multicofactor artificial enzymes.

| S-EPMC6650743 | biostudies-literature

Protonation and Proton-Coupled Electron Transfer at S-Ligated [4Fe-4S] Clusters.

Project description:Biological [Fe-S] clusters are increasingly recognized to undergo proton-coupled electron transfer (PCET), but the site of protonation, mechanism, and role for PCET remains largely unknown. Here we explore this reactivity with synthetic model clusters. Protonation of the arylthiolate-ligated [4Fe-4S] cluster [Fe4 S4 (SAr)4 ](2-) (1, SAr=S-2,4-6-(iPr)3 C6 H2 ) leads to thiol dissociation, reversibly forming [Fe4 S4 (SAr)3 L](1-) (2) and ArSH (L=solvent, and/or conjugate base). Solutions of 2+ArSH react with the nitroxyl radical TEMPO to give [Fe4 S4 (SAr)4 ](1-) (1ox ) and TEMPOH. This reaction involves PCET coupled to thiolate association and may proceed via the unobserved protonated cluster [Fe4 S4 (SAr)3 (HSAr)](1-) (1-H). Similar reactions with this and related clusters proceed comparably. An understanding of the PCET thermochemistry of this cluster system has been developed, encompassing three different redox levels and two protonation states.

| S-EPMC4646712 | biostudies-literature

Control of proton and electron transfer in de novo designed, biomimetic ? hairpins.

Project description:Tyrosine side chains are involved in proton coupled electron transfer reactions (PCET) in many complex proteins, including photosystem II (PSII) and ribonucleotide reductase. For example, PSII contains two redox-active tyrosines, TyrD (Y160D2) and TyrZ (Y161D1), which have different protein environments, midpoint potentials, and roles in catalysis. TyrD has a midpoint potential lower than that of TyrZ, and its protein environment is distinguished by potential ?-cation interactions with arginine residues. Designed biomimetic peptides provide a system that can be used to investigate how the protein matrix controls PCET reactions. As a model for the redox-active tyrosines in PSII, we are employing a designed, 18 amino acid ? hairpin peptide in which PCET reactions occur between a tyrosine (Tyr5) and a cross-strand histidine (His14). In this peptide, the single tyrosine is hydrogen-bonded to an arginine residue, Arg16, and a second arginine, Arg12, has a ?-cation interaction with Tyr5. In this report, the effect of these hydrogen bonding and electrostatic interactions on the PCET reactions is investigated. Electrochemical titrations show that histidine substitutions change the nature of PCET reactions, and optical titrations show that Arg16 substitution changes the pK of Tyr5. Removal of Arg16 or Arg12 increases the midpoint potential for tyrosine oxidation. The effects of Arg12 substitution are consistent with the midpoint potential difference, which is observed for the PSII redox-active tyrosine residues. Our results demonstrate that a ?-cation interaction, hydrogen bonding, and PCET reactions alter redox-active tyrosine function. These interactions can contribute equally to the control of midpoint potential and reaction rate.

| S-EPMC3042127 | biostudies-literature

Designed for life: biocompatible de novo designed proteins and components.

Project description:A principal goal of synthetic biology is the de novo design or redesign of biomolecular components. In addition to revealing fundamentally important information regarding natural biomolecular engineering and biochemistry, functional building blocks will ultimately be provided for applications including the manufacture of valuable products and therapeutics. To fully realize this ambitious goal, the designed components must be biocompatible, working in concert with natural biochemical processes and pathways, while not adversely affecting cellular function. For example, de novo protein design has provided us with a wide repertoire of structures and functions, including those that can be assembled and function in vivo Here we discuss such biocompatible designs, as well as others that have the potential to become biocompatible, including non-protein molecules, and routes to achieving full biological integration.

| S-EPMC6127164 | biostudies-literature

Theoretical study of DNA damage recognition via electron transfer from the [4Fe-4S] complex of MutY.

Project description:The mechanism of site-specific recognition of DNA by proteins has been a long-standing issue. The DNA glycosylase MutY, for instance, must find the rare 8-oxoguanine-adenine mismatches among the large number of basepairs in the DNA. This protein has a [4Fe-4S] cluster, which is highly conserved in species as diverse as Escherichia Coli and Homo sapiens. The mixed-valent nature of this cluster suggests that charge transfer may play a role in MutY's function. We have studied the energetics of the charge transfer in Bacillus stearothermophilus MutY-DNA complex using multiscale calculation including density functional theory and molecular dynamics. The [4Fe-4S] cluster in MutY is found to undergo 2+ to 3+ oxidation when coupling to DNA through hole transfer, especially when MutY is near an oxoguanine modified base (oxoG). Employing the Marcus theory for electron transfer, we find near optimal Frank-Condon factors for electron transfer from MutY to oxoguanine modified base. MutY has modest selectivity for oxoguanine over guanine due to the difference in oxidation potential. The tunneling matrix element is significantly reduced with the mutation R149W, whereas the mutation L154F reduces the tunneling matrix element as well as the Frank-Condon factor. Both L154F and R149W mutations are known to dramatically reduce or eliminate repair efficiency. We suggest a scenario where the charge transfer leads to a stabilization of the specific binding conformation, which is likely the recognition mode, thus enabling it to find the damaged site efficiently.

| S-EPMC2547449 | biostudies-literature

Electron transfer activity of a de novo designed copper center in a three-helix bundle fold.

Project description:In this work, we characterized the intermolecular electron transfer (ET) properties of a de novo designed metallopeptide using laser-flash photolysis. ?3D-CH3 is three helix bundle peptide that was designed to contain a copper ET site that is found in the ?-barrel fold of native cupredoxins. The ET activity of Cu?3D-CH3 was determined using five different photosensitizers. By exhibiting a complete depletion of the photo-oxidant and the successive formation of a Cu(II) species at 400 nm, the transient and generated spectra demonstrated an ET transfer reaction between the photo-oxidant and Cu(I)?3D-CH3. This observation illustrated our success in integrating an ET center within a de novo designed scaffold. From the kinetic traces at 400 nm, first-order and bimolecular rate constants of 10(5) s(-1) and 10(8) M(-1) s(-1) were derived. Moreover, a Marcus equation analysis on the rate versus driving force study produced a reorganization energy of 1.1 eV, demonstrating that the helical fold of ?3D requires further structural optimization to efficiently perform ET. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson.

| S-EPMC5233711 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data