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1.
Artigo em Inglês | MEDLINE | ID: mdl-32161212

RESUMO

In order to harness the functionality of metals, nature has evolved over billions of years to utilize metalloproteins as key components in numerous cellular processes. Despite this, transition metals such as ruthenium, palladium, iridium, and gold are largely absent from naturally occurring metalloproteins, likely due to their scarcity as precious metals. To mimic the evolutionary process of nature, the field of artificial metalloenzymes (ArMs) was born as a way to benefit from the unique chemoselectivity and orthogonality of transition metals in a biological setting. In its current state, numerous examples have successfully incorporated transition metals into a variety of protein scaffolds. Using these ArMs, many examples of new-to-nature reactions have been carried out, some of which have shown substantial biocompatibility. Given the rapid rate at which this field is growing, this review aims to highlight some important studies that have begun to take the next step within this field; namely the development of ArM-centered drug therapies or biotechnological tools.


Assuntos
Materiais Biomiméticos/química , Coenzimas/química , Metaloproteínas/química , Metais/química , Biocatálise , Técnicas Biossensoriais , Modelos Moleculares , Conformação Proteica , Engenharia de Proteínas , Estereoisomerismo
2.
Nat Commun ; 11(1): 862, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054841

RESUMO

Complex hierarchical structure governs emergent properties in biopolymeric materials; yet, the material processing involved remains poorly understood. Here, we investigated the multi-scale structure and composition of the mussel byssus cuticle before, during and after formation to gain insight into the processing of this hard, yet extensible metal cross-linked protein composite. Our findings reveal that the granular substructure crucial to the cuticle's function as a wear-resistant coating of an extensible polymer fiber is pre-organized in condensed liquid phase secretory vesicles. These are phase-separated into DOPA-rich proto-granules enveloped in a sulfur-rich proto-matrix which fuses during secretion, forming the sub-structure of the cuticle. Metal ions are added subsequently in a site-specific way, with iron contained in the sulfur-rich matrix and vanadium coordinated by DOPA-catechol in the granule. We posit that this hierarchical structure self-organizes via phase separation of specific amphiphilic proteins within secretory vesicles, resulting in a meso-scale structuring that governs cuticle function.


Assuntos
Materiais Revestidos Biocompatíveis/química , Metaloproteínas/química , Mytilus edulis/química , Estruturas Animais/anatomia & histologia , Estruturas Animais/química , Estruturas Animais/ultraestrutura , Animais , Di-Hidroxifenilalanina/química , Imageamento Tridimensional , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Mytilus edulis/anatomia & histologia , Mytilus edulis/ultraestrutura , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Vesículas Secretórias/química , Vesículas Secretórias/ultraestrutura
3.
Nat Commun ; 11(1): 316, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949281

RESUMO

Here we propose an experimental setup based on operando X-ray absorption spectroscopy (XAS) to understand why copper-containing oxidoreductase enzymes show exceptional performance as catalysts for the oxygen reduction reaction (ORR). An electrode based on carbon nanoparticles organized in mesoporous structures with bilirubin oxidase (BOD) was developed to be used in a home-made operando XAS electrochemical cell, and we probed the electron transfer under ORR regime. In the presence of molecular oxygen, the BOD cofactor containing 4 copper ions require an overpotential about 150 mV to be reduced as compared to that in the absence of oxygen. A second electron transfer step, which occurs faster than the cofactor reduction, suggests that the cooper ions act as a tridimensional redox active electronic bridges for the electron transfer reaction.


Assuntos
Cobre/química , Transporte de Elétrons , Elétrons , Metaloproteínas/química , Oxirredutases/química , Espectroscopia por Absorção de Raios X/métodos , Catálise , Eletrodos , Modelos Químicos , Oxirredução , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química , Oxigênio/química , Saccharomycetales
4.
Inorg Chem ; 59(1): 214-225, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31814403

RESUMO

Formate dehydrogenase (FDH) enzymes are versatile catalysts for CO2 conversion. The FDH from Rhodobacter capsulatus contains a molybdenum cofactor with the dithiolene functions of two pyranopterin guanine dinucleotide molecules, a conserved cysteine, and a sulfido group bound at Mo(VI). In this study, we focused on metal oxidation state and coordination changes in response to exposure to O2, inhibitory anions, and redox agents using X-ray absorption spectroscopy (XAS) at the Mo K-edge. Differences in the oxidative modification of the bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor relative to samples prepared aerobically without inhibitor, such as variations in the relative numbers of sulfido (Mo═S) and oxo (Mo═O) bonds, were observed in the presence of azide (N3-) or cyanate (OCN-). Azide provided best protection against O2, resulting in a quantitatively sulfurated cofactor with a displaced cysteine ligand and optimized formate oxidation activity. Replacement of the cysteine ligand by a formate (HCO2-) ligand at the molybdenum in active enzyme is compatible with our XAS data. Cyanide (CN-) inactivated the enzyme by replacing the sulfido ligand at Mo(VI) with an oxo ligand. Evidence that the sulfido group may become protonated upon molybdenum reduction was obtained. Our results emphasize the role of coordination flexibility at the molybdenum center during inhibitory and catalytic processes of FDH enzymes.


Assuntos
Coenzimas/química , Formiato Desidrogenases/química , Metaloproteínas/química , Pteridinas/química , Rhodobacter capsulatus/enzimologia , Ânions/química , Ânions/metabolismo , Sítios de Ligação , Coenzimas/metabolismo , Formiato Desidrogenases/isolamento & purificação , Formiato Desidrogenases/metabolismo , Metaloproteínas/metabolismo , Oxirredução , Pteridinas/metabolismo , Espectroscopia por Absorção de Raios X
5.
Chemistry ; 26(1): 249-258, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31710732

RESUMO

Superoxide dismutases (SODs) are highly efficient enzymes for superoxide dismutation and the first line of defense against oxidative stress. These metalloproteins contain a redox-active metal ion in their active site (Mn, Cu, Fe, Ni) with a tightly controlled reduction potential found in a close range around the optimal value of 0.36 V versus the normal hydrogen electrode (NHE). Rationally designed proteins with well-defined three-dimensional structures offer new opportunities for obtaining functional SOD mimics. Here, we explore four different copper-binding scaffolds: H3 (His3 ), H4 (His4 ), H2 DH (His3 Asp with two His and one Asp in the same plane) and H3 D (His3 Asp with three His in the same plane) by using the scaffold of the de novo protein GRα3 D. EPR and XAS analysis of the resulting copper complexes demonstrates that they are good CuII -bound structural mimics of Cu-only SODs. Furthermore, all the complexes exhibit SOD activity, though three orders of magnitude slower than the native enzyme, making them the first de novo copper SOD mimics.


Assuntos
Cobre/química , Metaloproteínas/química , Peptídeos/química , Sequência de Aminoácidos , Cobre/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Ensaios Enzimáticos , Metaloproteínas/metabolismo , Peptídeos/metabolismo , Estabilidade Proteica , Superóxido Dismutase/química , Superóxido Dismutase/metabolismo , Temperatura , Termodinâmica
6.
Inorg Chem ; 59(1): 790-800, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31829577

RESUMO

Investigation of the diverse evolutionary developed mechanisms enabling bacteria to maintain homeostasis and to be resistant to lead is crucial for the discovery of novel strategies for isolation of this highly toxic metal and its subsequent elimination from contaminated environments. The metalloregulatory protein pbrR and its homologues that were identified in the Cupriavidus metallidurans CH34 chromosome are the only characterized natural metalloproteins that have a special affinity toward Pb(II) and that bind it with at least a 1000-fold selectivity over other heavy metals. The X-ray structures of apo and Pb(II)-bound pbrR have been recently reported. In the present study, the binding of Pb(II) at pbrR was investigated by means of multiscale computational modeling. Molecular dynamics simulations substantiated how conformations amenable for the Pb(II) complexation through the tris-cysteine motif are formed from the antiparallel coiled-coil packing interaction of two dimerization helices of two pbrR monomers, and the phase space of apo-pbrR has been extensively sampled. Hybrid quantum mechanics/molecular mechanics (QM/MM) calculations on metal-bound structures of pbrR also allowed us to determine the most probable protonation state for the lead binding motif and evaluate the structural features mostly affecting the Pb(II) coordination in this protein. In agreement with available experimental data, we found that pbrR may control its Pb(II) affinity, probably, by conformational changes that affect the distance between Cys78' and Cys122 and their protonation states, thus being able to switch on the Pb(II) sequestration/release-prone states in response to external stimuli. The protein structure enveloping the metal binding motif favors the thiol-thiolate-thiolate protonation state of Pb(II)-pbrR, thus probably enhancing the binding selectivity for Pb(II), compared to other metal ions.


Assuntos
Cupriavidus/química , Chumbo/análise , Metaloproteínas/química , Simulação de Dinâmica Molecular , Teoria Quântica
7.
Biochim Biophys Acta Bioenerg ; 1861(1): 148118, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31734195

RESUMO

CO dehydrogenase (CODH) from the Gram-negative bacterium Oligotropha carboxidovorans is a complex metalloenzyme from the xanthine oxidase family of molybdenum-containing enzymes, bearing a unique binuclear Mo-S-Cu active site in addition to two [2Fe-2S] clusters (FeSI and FeSII) and one equivalent of FAD. CODH catalyzes the oxidation of CO to CO2 with the concomitant introduction of reducing equivalents into the quinone pool, thus enabling the organism to utilize CO as sole source of both carbon and energy. Using a variety of EPR monitored redox titrations and spectroelectrochemistry, we report the redox potentials of CO dehydrogenase at pH 7.2 namely MoVI/V, MoV/IV, FeSI2+/+, FeSII2+/+, FAD/FADH and FADH/FADH-. These potentials are systematically higher than the corresponding potentials seen for other members of the xanthine oxidase family of Mo enzymes, and are in line with CODH utilising the higher potential quinone pool as an electron acceptor instead of pyridine nucleotides. CODH is also active when immobilised on a modified Au working electrode as demonstrated by cyclic voltammetry in the presence of CO.


Assuntos
Aldeído Oxirredutases/química , Bradyrhizobiaceae/enzimologia , Metaloproteínas/química , Complexos Multienzimáticos/química , Aldeído Oxirredutases/metabolismo , Catálise , Domínio Catalítico , Cobalto/química , Cobalto/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Flavina-Adenina Dinucleotídeo/química , Flavina-Adenina Dinucleotídeo/metabolismo , Metaloproteínas/metabolismo , Molibdênio/química , Molibdênio/metabolismo , Complexos Multienzimáticos/metabolismo
8.
Phys Chem Chem Phys ; 21(42): 23408-23417, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31625550

RESUMO

In the field of artificial metalloenzyme (ArM) catalysis, how to identify the critical factors affecting the catalytic activity and enantioselectivity remains a challenge. In this work, the mechanism of enantioselective reduction of imine catalyzed by using [Rh(Me4Cpbiot)Cl2]·S112H Sav (denoted as S112H) and [Rh(Me4Cpbiot)Cl2]·K121H Sav (denoted as K121H) was studied by using molecular dynamics (MD) simulations combined with density functional theory (DFT) calculations. Four binding modes of imine, two proton sources (hydronium ion and lysine) and eight proposed reaction pathways were systematically discussed. The results showed that due to the anchoring effect of the mutation site of ArMs, the rhodium complex which oscillated like a pendulum was bound to a specific conformation, which further determined the chirality of the reduced product. C-Hπ, cation-π and ππ weak interactions played an important role in imine binding, and the favorable binding mode of imine was catalyzed by S112H in landscape orientation and catalyzed by K121H in portrait orientation, respectively. LYS121 is the most possible proton source in the S112H catalytic process while the proton source in the K121H catalytic process is the hydronium ion of the active sites. Furthermore, based on the reaction mechanism, modification of Rh(Me4Cpbiot)Cl2 was carried out in S112H and K121H, and the results suggested that the reaction barrier could be effectively reduced by replacing the methyl groups on Cp* with an amino group. This work gives a fundamental understanding of the mechanism of ArMs toward the imine reduction reaction, in the hope of providing a strategy for reasonable designs of ArMs with high enantioselectivity.


Assuntos
Complexos de Coordenação/química , Iminas/química , Sítios de Ligação , Catálise , Domínio Catalítico , Complexos de Coordenação/metabolismo , Teoria da Densidade Funcional , Metaloproteínas/química , Metaloproteínas/metabolismo , Simulação de Dinâmica Molecular , Oxirredução , Ródio/química , Estereoisomerismo , Termodinâmica
9.
Chemistry ; 25(67): 15252-15256, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31509280

RESUMO

Metalloenzymes often utilize radicals in order to facilitate chemical reactions. Recently, DeGrado and co-workers have discovered that model proteins can efficiently stabilize semiquinone radical anion produced by oxidation of 3,5-di-tert-butylcatechol (DTBC) in the presence of two zinc ions. Here, we show that the number and the nature of metal ions have relatively minor effect on semiquinone stabilization in model proteins, with a single metal ion being sufficient for radical stabilization. The radical is stabilized by both metal ion, hydrophobic sequestration, and interactions with the hydrophilic residues in the protein interior resulting in a remarkable, nearly 500 mV change in the redox potential of the SQ. - /catechol couple compared to bulk aqueous solution. Moreover, we have created 4G-UFsc, a single metal ion-binding protein with pm affinity for zinc that is higher than any other reported model systems and is on par with many natural zinc-containing proteins. We expect that the robust and easy-to-modify DFsc/UFsc family of proteins will become a versatile tool for mechanistic model studies of metalloenzymes.


Assuntos
Benzoquinonas/química , Metaloproteínas/química , Metais/química , Sequência de Aminoácidos , Sítios de Ligação , Catecóis/química , Interações Hidrofóbicas e Hidrofílicas , Íons/química , Cinética , Ligantes , Modelos Moleculares , Oxirredução , Ligação Proteica , Conformação Proteica , Estabilidade Proteica/efeitos dos fármacos , Termodinâmica
10.
Int J Mol Sci ; 20(16)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398861

RESUMO

The work presents the kinetic and isotherm studies of silver binding on casein, which was carried out using batch sorption technique. Moreover, the influence of light irradiation on the process was shown. In order to investigate the mechanism of metal ions sorption by casein the zero, pseudo-first order kinetics and Weber-Morris intra-particle diffusion as well as Langmuir and Freundlich isotherm models were used. Furthermore, to specify more precisely, the possible binding mechanism, the spectroscopic (FT-IR-Fourier Transform Infrared Spectroscopy, Raman), spectrometric (MALDI-TOF MS-Matrix-Assisted Laser Desorption/Ionization Time Of Flight Mass Spectrometry), microscopic (SEM-Scanning Electron Microscope, TEM/EDX-Transmission Electron Microscopy/Energy Dispersive X-ray detector) and thermal (TGA-Thermogravimetric Analysis, DTG-Derivative Thermogravimetry) analysis were performed. Kinetic study indicates that silver binding onto casein is a heterogeneous process with two main stages: initial rapid stage related to surface adsorption onto casein with immediate creation of silver nanoparticles and slower second stage of intraglobular diffusion with silver binding in chelated form (metalloproteins) or ion-exchange form. Spectroscopic techniques confirmed the binding process and MALDI-TOF MS analysis show the dominant contribution of the α-casein in the process. Moreover, the treatment of silver-casein complex by artificial physiological fluids was performed.


Assuntos
Caseínas/química , Íons/química , Prata/química , Concentração de Íons de Hidrogênio , Cinética , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Metaloproteínas/química , Modelos Teóricos , Ligação Proteica , Análise Espectral , Termodinâmica , Termogravimetria
11.
Molecules ; 24(15)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362341

RESUMO

Metalloproteins and metalloenzymes play important roles in biological systems by using the limited metal ions, complexes, and clusters that are associated with the protein matrix. The design of artificial metalloproteins and metalloenzymes not only reveals the structure and function relationship of natural proteins, but also enables the synthesis of artificial proteins and enzymes with improved properties and functions. Acknowledging the progress in rational design from single to multiple active sites, this review focuses on recent achievements in the design of artificial metalloproteins and metalloenzymes with metal clusters, including zinc clusters, cadmium clusters, iron-sulfur clusters, and copper-sulfur clusters, as well as noble metal clusters and others. These metal clusters were designed in both native and de novo protein scaffolds for structural roles, electron transfer, or catalysis. Some synthetic metal clusters as functional models of native enzymes are also discussed. These achievements provide valuable insights for deep understanding of the natural proteins and enzymes, and practical clues for the further design of artificial enzymes with functions comparable or even beyond those of natural counterparts.


Assuntos
Enzimas/química , Metaloproteínas/química , Metais/química , Engenharia de Proteínas , Proteínas de Transporte , Catálise , Domínio Catalítico , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ligação Proteica
13.
Inorg Chem ; 58(20): 13673-13685, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31298530

RESUMO

The clinical application and development of potent metal-based drugs relies heavily on a full understanding of their underlying molecular mechanisms. The emerging research field of metalloproteomics for unveiling the correlation between metals and biological proteomes has received growing attention and has been successfully implemented in medicinal inorganic chemistry. In this article, we introduce recent progress in the mechanistic studies of representative metal-based drugs by using state-of-the-art metalloproteomic approaches, with a focus on how the application of analytical chemistry, biocompatible chemical probes, and integrative omics help to advance the knowledge of metallodrug targeting profiles within a systemic perspective.


Assuntos
Complexos de Coordenação/metabolismo , Metaloproteínas/metabolismo , Metais/metabolismo , Preparações Farmacêuticas/metabolismo , Proteômica , Complexos de Coordenação/química , Metaloproteínas/química , Metais/química , Estrutura Molecular , Preparações Farmacêuticas/química
14.
Org Biomol Chem ; 17(30): 7114-7123, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31294731

RESUMO

This review describes the recent advances in the design of novel artificial metalloenzymes and their application in C-H activation reactions. The combination of enzymes and metal or organometallic complexes for the creation of new artificial metalloenzymes has represented a very exciting research line. In particular, the development of proteins with the ability to perform C-H functionalization presents a significant challenge. Here we discuss the development of these processes on natural metalloenzymes by using directed evolution, biotin-(strept)avidin technologies, photocatalytic hybrids or reconstitution of heme-protein technology.


Assuntos
Metaloproteínas/antagonistas & inibidores , Compostos Organometálicos/farmacologia , Metaloproteínas/síntese química , Metaloproteínas/química , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química
15.
J Chem Theory Comput ; 15(8): 4602-4614, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31268700

RESUMO

Many biological processes are based on molecular recognition between highly charged molecules such as nucleic acids, inorganic ions, charged amino acids, etc. For such cases, it has been demonstrated that molecular simulations with fixed partial charges often fail to achieve experimental accuracy. Although incorporation of more advanced electrostatic models (such as multipoles, mutual polarization, etc.) can significantly improve simulation accuracy, it increases computational expense by a factor of 5-20×. Indirect free energy (IFE) methods can mitigate this cost by modeling intermediate states at fixed-charge resolution. For example, an efficient "reference" model such as a pairwise Amber, CHARMM, or OPLS-AA force field can be used to derive an initial estimate, followed by thermodynamic corrections to a more advanced "target" potential such as the polarizable AMOEBA model. Unfortunately, all currently described IFE methods encounter difficulties reweighting more than ∼50 atoms between resolutions due to extensive scaling of both the magnitude of the thermodynamic corrections and their statistical uncertainty. We present an approach called "simultaneous bookending" (SB) that is fundamentally different from existing IFE methods based on a tunable sampling approximation, which permits scaling to thousands of atoms. SB is demonstrated on the relative binding affinity of Mg2+/Ca2+ to a set of metalloproteins with up to 2972 atoms, finding no statistically significant difference between direct AMOEBA results and those from correcting Amber to AMOEBA. The ability to change the resolution of thousands of atoms during reweighting suggests the approach may be applicable in the future to protein-protein binding affinities or nucleic acid thermodynamics.


Assuntos
Cálcio/metabolismo , Cátions Bivalentes/metabolismo , Magnésio/metabolismo , Metaloproteínas/metabolismo , Animais , Cálcio/química , Cátions Bivalentes/química , Bases de Dados de Proteínas , Humanos , Magnésio/química , Metaloproteínas/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Software , Eletricidade Estática , Termodinâmica
16.
Int J Mol Sci ; 20(13)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288391

RESUMO

Dimethyl sulfoxide reductases (DMSO) are molybdoenzymes widespread in all domains of life. They catalyse not only redox reactions, but also hydroxylation/hydration and oxygen transfer processes. Although literature on DMSO is abundant, the biological significance of these enzymes in anaerobic respiration and the molecular mechanisms beyond the expression of genes coding for them are still scarce. In this review, a deep revision of the literature reported on DMSO as well as the use of bioinformatics tools and free software has been developed in order to highlight the relevance of DMSO reductases on anaerobic processes connected to different biogeochemical cycles. Special emphasis has been addressed to DMSO from extremophilic organisms and their role in nitrogen cycle. Besides, an updated overview of phylogeny of DMSOs as well as potential applications of some DMSO reductases on bioremediation approaches are also described.


Assuntos
Extremófilos , Proteínas com Ferro-Enxofre/genética , Proteínas com Ferro-Enxofre/metabolismo , Isoenzimas , Família Multigênica , Oxirredutases/genética , Oxirredutases/metabolismo , Filogenia , Coenzimas/química , Coenzimas/metabolismo , Extremófilos/genética , Extremófilos/metabolismo , Proteínas com Ferro-Enxofre/química , Redes e Vias Metabólicas , Metaloproteínas/química , Metaloproteínas/metabolismo , Molibdênio/química , Molibdênio/metabolismo , Ciclo do Nitrogênio , Oxirredução , Oxirredutases/química , Pteridinas/química , Pteridinas/metabolismo , Relação Estrutura-Atividade , Tungstênio/química , Tungstênio/metabolismo
17.
Molecules ; 24(13)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277490

RESUMO

Nature has tailored a wide range of metalloenzymes that play a vast array of functions in all living organisms and from which their survival and evolution depends on. These enzymes catalyze some of the most important biological processes in nature, such as photosynthesis, respiration, water oxidation, molecular oxygen reduction, and nitrogen fixation. They are also among the most proficient catalysts in terms of their activity, selectivity, and ability to operate at mild conditions of temperature, pH, and pressure. In the absence of these enzymes, these reactions would proceed very slowly, if at all, suggesting that these enzymes made the way for the emergence of life as we know today. In this review, the structure and catalytic mechanism of a selection of diverse metalloenzymes that are involved in the production of highly reactive and unstable species, such as hydroxide anions, hydrides, radical species, and superoxide molecules are analyzed. The formation of such reaction intermediates is very difficult to occur under biological conditions and only a rationalized selection of a particular metal ion, coordinated to a very specific group of ligands, and immersed in specific proteins allows these reactions to proceed. Interestingly, different metal coordination spheres can be used to produce the same reactive and unstable species, although through a different chemistry. A selection of hand-picked examples of different metalloenzymes illustrating this diversity is provided and the participation of different metal ions in similar reactions (but involving different mechanism) is discussed.


Assuntos
Enzimas/metabolismo , Metaloproteínas/química , Catálise , Hidróxidos/química , Superóxidos/química
18.
Inorg Chem ; 58(16): 11091-11099, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31353893

RESUMO

Several bacterial species have evolutionary developed protein systems specialized in the control of intracellular gold ion concentration. In order to prevent the detrimental consequences that may be induced even at very low concentrations, bacteria such as Salmonella enterica and Cupriavidus metallidurans utilize Au-specific merR-type transcriptional regulators that detect these toxic ions and control the expression of specific resistance factors. Among these highly specialized proteins, golB has been investigated in depth, and X-ray structures of both apo and Au(I)-bound golB have been recently reported. Here, the binding of Au(I) at golB was investigated by means of multilevel computational approaches. Molecular dynamics simulations evidenced how conformations amenable for the Au(I) chelation through the Cys-XX-Cys motif on helix 1 are extensively sampled in the phase space of apo-golB. Hybrid QM/MM calculations on metal-bound structures of golB also allowed to characterize the most probable protonation state for gold binding motif and to assess the structural features mostly influencing the Au(I) coordination in this protein. Consistently with experimental evidence, we found that golB may control its Au(I) affinity by conformational changes that affect the distance between Cys10 and Cys13, thus being able to switch between the Au(I) sequestration/release-prone states in response to external stimuli. The protein structure enveloping the metal binding motif favors the thiol-thiolate protonation state of Au(I)-golB, thus probably enhancing the binding selectivity for Au(I) compared to other cations.


Assuntos
Proteínas de Bactérias/química , Ouro/química , Metaloproteínas/química , Simulação de Dinâmica Molecular , Teoria Quântica , Cupriavidus/química , Salmonella enterica/química
19.
Chem Commun (Camb) ; 55(54): 7752-7755, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31204733

RESUMO

Metal-binding peptides are versatile building blocks in supramolecular chemistry. We recently reported a class of crystalline materials formed through a combination of coiled-coil peptide self-association and metal coordination. Here, we probe the serendipitously discovered metal binding motif that drives the assembly and apply these insights to exert rational control over structure and morphology in the materials.


Assuntos
Metaloproteínas/química , Motivos de Aminoácidos , Sequência de Aminoácidos , Cobre/química , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Metaloproteínas/síntese química , Engenharia de Proteínas/métodos , Multimerização Proteica , Piridinas/química
20.
Biophys Chem ; 252: 106207, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31252378

RESUMO

Conformational changes in bio-molecular systems are fundamental to several biological processes. It is important to study changes in responses of underlying microscopic variables, like dihedral angles as conformational change takes place. We perform all-atom simulations and modelling via Langevin equation to illustrate the changes in structural and dynamic responses of dihedral angles of calcium ion binding residues of different proteins in metal ion free (apo) and bound (holo) states. The equilibrium distributions of dihedral angles in apo- and holo-states represent structural response. Our studies show the presence of dihedrals with multiple peaks (isomeric states) separated by barrier heights is more frequent in apo- than in holo-state. The relaxation time-scale of dihedral fluctuations is found to increase linearly with decreasing barrier height due to more frequent barrier re-crossing events. The slow kinetic response of the dihedrals also contributes to slowing down of macro-scale fluctuations, which may be useful to understand kinetics of various bio-molecular processes.


Assuntos
Cálcio/metabolismo , Metaloproteínas/química , Metaloproteínas/metabolismo , Simulação de Dinâmica Molecular , Sítios de Ligação , Cálcio/química , Íons/química , Íons/metabolismo , Conformação Proteica
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