Shape and size complementarity induced formation of supramolecular protein assemblies with metal-oxo clusters

AbstractThe controlled formation of protein supramolecular assemblies is challenging but it could provide an important route for the development of hybrid biomaterials. In this work, we demonstrate formation of well-defined complexes formed between the 8-fold symmetrical designer protein Tako8 and soluble metal-oxo clusters from the family of Anderson-Evans, Keggin and ZrIV- substituted Wells-Dawson polyoxometalates. A combination of x-ray crystallography and solution studies showed that metal-oxo clusters are able to serve as linker nodes for the bottom-up creation of protein based supramolecular assemblies. Our findings indicate that clusters with larger size and negative charge are capable of modulating the crystal packing of the protein, highlighting the need for a size and shape complementarity with the protein node for optimal alteration of the crystalline self-assembly.

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Effect of the proximal secondary sphere on the self-assembly of tetrahedral zinc-oxo clusters

Communications Chemistry ◽

10.1038/s42004-021-00574-3 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Michał Terlecki ◽

Iwona Justyniak ◽

Michał K. Leszczyński ◽

Janusz Lewiński

Keyword(s):

Coordination Sphere ◽

Self Assembly ◽

Rational Design ◽

Supramolecular Assemblies ◽

The Self ◽

Intermolecular Hydrogen Bonds ◽

Secondary Coordination Sphere ◽

Catalytic Sites ◽

Solid State Structures ◽

Metal Oxo Clusters

AbstractMetal-oxo clusters can serve as directional and rigid building units of coordination and noncovalent supramolecular assemblies. Therefore, an in-depth understanding of their multi-faceted chemistry is vital for the development of self-assembled solid-state structures of desired properties. Here we present a comprehensive comparative structural analysis of isostructural benzoate, benzamidate, and new benzamidinate zinc-oxo clusters incorporating the [O,O]-, [O,NH]- and [NH,NH]-anchoring donor centers, respectively. We demonstrated that the NH groups in the proximal secondary coordination sphere are prone to the formation of intermolecular hydrogen bonds, which affects the packing of clusters in the crystal structure. Coordination sphere engineering can lead to the rational design of new catalytic sites and novel molecular building units of supramolecular assemblies.

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Self-assembly modes of glycyrrhetinic acid esters in view of the crystal packing of related triterpene molecules

Acta Crystallographica Section B Structural Science Crystal Engineering and Materials ◽

10.1107/s2052520616008180 ◽

2016 ◽

Vol 72 (4) ◽

pp. 584-592

Author(s):

Dominik Langer ◽

Barbara Wicher ◽

Wojciech Szczołko ◽

Maria Gdaniec ◽

Ewa Tykarska

Keyword(s):

Self Assembly ◽

Crystal Packing ◽

Glycyrrhetinic Acid ◽

Cooh Group ◽

Supramolecular Organization ◽

X Ray ◽

X Ray Crystallography ◽

Solvent Molecules ◽

Derivatives Of ◽

Acid Esters

The crystal structures of three ester derivatives of glycyrrhetinic acid (GE) are reported. X-ray crystallography revealed that despite differences in the size of the ester substituents (ethyl, isopropyl and 2-morpholinoethyl) the scheme of molecular self-assembly is similar in all three cases but differs significantly from that observed in other known GE esters. According to our analysis, the two basic patterns of self-assembly of GE esters observed in their unsolvated crystals correspond to two distinct orientations of the ester groups relative to the triterpene backbone. Moreover, comparison of the self-assembly modes of GE esters in their unsolvated forms with the supramolecular organization of GE and carbenoxolone in their solvated crystals revealed that ester substituents replace solvent molecules hydrogen bonded to the COOH group at the triterpene skeleton, resulting in similar packing arrangements of these compounds.

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Shape Complementarity Modulated Self-Assembly of Nanoring and Nanosphere Hetero-nanostructures

Journal of the American Chemical Society ◽

10.1021/jacs.0c04678 ◽

2020 ◽

Vol 142 (27) ◽

pp. 11680-11684

Author(s):

Na Li ◽

Fan Wu ◽

Zihong Han ◽

Xiaofeng Wang ◽

Yi Liu ◽

...

Keyword(s):

Self Assembly ◽

Shape Complementarity

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Estimating the shape and size of supramolecular assemblies by variable temperature diffusion ordered spectroscopy

Organic & Biomolecular Chemistry ◽

10.1039/c4ob01373e ◽

2014 ◽

Vol 12 (40) ◽

pp. 7932-7936 ◽

Cited By ~ 23

Author(s):

Benjamin M. Schulze ◽

Davita L. Watkins ◽

Jing Zhang ◽

Ion Ghiviriga ◽

Ronald K. Castellano

Keyword(s):

Self Assembly ◽

Variable Temperature ◽

Supramolecular Assemblies ◽

The Self ◽

Conjugated Oligomers ◽

Photovoltaic Devices ◽

Temperature Diffusion ◽

Shape And Size

Reported is characterization of the self-assembly of π-conjugated oligomers, molecules studied recently in photovoltaic devices, using variable temperature diffusion ordered spectroscopy; the approach has allowed estimation of assembly size, shape, and molecularity.

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Examining the structure of the mature amyloid fibril

Biochemical Society Transactions ◽

10.1042/bst0300521 ◽

2002 ◽

Vol 30 (4) ◽

pp. 521-525 ◽

Cited By ~ 43

Author(s):

O. S. Makin ◽

L. C. Serpell

Keyword(s):

Self Assembly ◽

Rational Design ◽

Amyloid Fibrils ◽

Structural Information ◽

X Ray ◽

X Ray Crystallography ◽

Cryo Electron Microscopy ◽

Fibre Diffraction ◽

Complementary Techniques ◽

Mature Fibril

The pathogenesis of the group of diseases known collectively as the amyloidoses is characterized by the deposition of insoluble amyloid fibrils. These are straight, unbranching structures about 70–120 å (1 å = 0.1 nm) in diameter and of indeterminate length formed by the self-assembly of a diverse group of normally soluble proteins. Knowledge of the structure of these fibrils is necessary for the understanding of their abnormal assembly and deposition, possibly leading to the rational design of therapeutic agents for their prevention or disaggregation. Structural elucidation is impeded by fibril insolubility and inability to crystallize, thus preventing the use of X-ray crystallography and solution NMR. CD, Fourier-transform infrared spectroscopy and light scattering have been used in the study of the mechanism of fibril formation. This review concentrates on the structural information about the final, mature fibril and in particular the complementary techniques of cryo-electron microscopy, solid-state NMR and X-ray fibre diffraction.

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Molecular mechanism of ATP versus GTP selectivity of adenylate kinase

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1721508115 ◽

2018 ◽

Vol 115 (12) ◽

pp. 3012-3017 ◽

Cited By ~ 11

Author(s):

Per Rogne ◽

Marie Rosselin ◽

Christin Grundström ◽

Christian Hedberg ◽

Uwe H. Sauer ◽

...

Keyword(s):

Hydrogen Bond ◽

Adenylate Kinase ◽

Function Analysis ◽

Substrate Selectivity ◽

Cellular Functions ◽

X Ray ◽

Precise Control ◽

X Ray Crystallography ◽

The Family ◽

Atp Analogs

Enzymatic substrate selectivity is critical for the precise control of metabolic pathways. In cases where chemically related substrates are present inside cells, robust mechanisms of substrate selectivity are required. Here, we report the mechanism utilized for catalytic ATP versus GTP selectivity during adenylate kinase (Adk) -mediated phosphorylation of AMP. Using NMR spectroscopy we found that while Adk adopts a catalytically competent and closed structural state in complex with ATP, the enzyme is arrested in a catalytically inhibited and open state in complex with GTP. X-ray crystallography experiments revealed that the interaction interfaces supporting ATP and GTP recognition, in part, are mediated by coinciding residues. The mechanism provides an atomic view on how the cellular GTP pool is protected from Adk turnover, which is important because GTP has many specialized cellular functions. In further support of this mechanism, a structure–function analysis enabled by synthesis of ATP analogs suggests that a hydrogen bond between the adenine moiety and the backbone of the enzyme is vital for ATP selectivity. The importance of the hydrogen bond for substrate selectivity is likely general given the conservation of its location and orientation across the family of eukaryotic protein kinases.

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Are GPCRs Still a Source of New Targets?

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057113498418 ◽

2013 ◽

Vol 18 (9) ◽

pp. 947-966 ◽

Cited By ~ 110

Author(s):

Stephen L. Garland

Keyword(s):

Drug Targets ◽

Protein Complexes ◽

X Ray Crystallography ◽

Peptide Family ◽

Wide Range ◽

The Family ◽

Receptor Pharmacology ◽

Technical Advances ◽

Allosteric Mechanisms ◽

G Protein Coupled

G-protein–coupled receptors (GPCRs) still offer enormous scope for new therapeutic targets. Currently marketed agents are dominated by those with activity at aminergic receptors and yet they account for only ~10% of the family. Progress up until now with other subfamilies, notably orphans, Family A/peptide, Family A/lipid, Family B, Family C, and Family F, has been, at best, patchy. This may be attributable to the heterogeneous nature of GPCRs, their endogenous ligands, and consequently their binding sites. Our appreciation of receptor similarity has arguably been too simplistic, and screening collections have not necessarily been well suited to identifying leads in new areas. Despite the relative shortage of high-quality tool molecules in a number of cases, there is an emerging, and increasingly substantial, body of evidence associating many as yet “undrugged” receptors with a very wide range of diseases. Significant advances in our understanding of receptor pharmacology and technical advances in screening, protein X-ray crystallography, and ligand design methods are paving the way for new successes in the area. Exploitation of allosteric mechanisms; alternative signaling pathways such as G12/13, Gβγ, and β-arrestin; the discovery of “biased” ligands; and the emergence of GPCR-protein complexes as potential drug targets offer scope for new and much improved drugs.

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Structural and functional properties of a magnesium transporter of the SLC11/NRAMP family

eLife ◽

10.7554/elife.74589 ◽

2022 ◽

Vol 11 ◽

Author(s):

Karthik Ramanadane ◽

Monique S Straub ◽

Raimund Dutzler ◽

Cristina Manatschal

Keyword(s):

Hydration Shell ◽

Transition Metal Ions ◽

Ion Binding ◽

X Ray ◽

X Ray Crystallography ◽

Protein Architecture ◽

Large Pool ◽

Structural And Functional Properties ◽

The Family ◽

Magnesium Transporter

Members of the ubiquitous SLC11/NRAMP family catalyze the uptake of divalent transition metal ions into cells. They have evolved to efficiently select these trace elements from a large pool of Ca2+ and Mg2+, which are both orders of magnitude more abundant, and to concentrate them in the cytoplasm aided by the cotransport of H+ serving as energy source. In the present study, we have characterized a member of a distant clade of the family found in prokaryotes, termed NRMTs, that were proposed to function as transporters of Mg2+. The protein transports Mg2+ and Mn2+ but not Ca2+ by a mechanism that is not coupled to H+. Structures determined by cryo-EM and X-ray crystallography revealed a generally similar protein architecture compared to classical NRAMPs, with a restructured ion binding site whose increased volume provides suitable interactions with ions that likely have retained much of their hydration shell.

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The Research of G–Motif Construction and Chirality in Deoxyguanosine Monophosphate Nucleotide Complexes

Frontiers in Chemistry ◽

10.3389/fchem.2021.709777 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yanhong Zhu ◽

Zhongkui Li ◽

Pengfei Wang ◽

Qi–Ming Qiu ◽

Hongwei Ma ◽

...

Keyword(s):

Solid State ◽

Self Assembly ◽

Genetic Diseases ◽

Dna Interaction ◽

Wave Direction ◽

Base Pairing ◽

X Ray Crystallography ◽

Mismatched Dna ◽

H Nmr ◽

Guanine Base

A detailed understanding of the mismatched base-pairing interactions in DNA will help reveal genetic diseases and provide a theoretical basis for the development of targeted drugs. Here, we utilized mononucleotide fragment to simulate mismatch DNA interactions in a local hydrophobic microenvironment. The bipyridyl-type bridging ligands were employed as a mild stabilizer to stabilize the GG mismatch containing complexes, allowing mismatch to be visualized based on X-ray crystallography. Five single crystals of 2′-deoxyguanosine–5′–monophosphate (dGMP) metal complexes were designed and obtained via the process of self-assembly. Crystallographic studies clearly reveal the details of the supramolecular interaction between mononucleotides and guest intercalators. A novel guanine–guanine base mismatch pattern with unusual (high anti)–(high anti) type of arrangement around the glycosidic angle conformations was successfully constructed. The solution state 1H–NMR, ESI–MS spectrum studies, and UV titration experiments emphasize the robustness of this g–motif in solution. Additionally, we combined the methods of single-crystal and solution-, solid-state CD spectrum together to discuss the chirality of the complexes. The complexes containing the g–motif structure, which reduces the energy of the system, following the solid-state CD signals, generally move in the long-wave direction. These results provided a new mismatched base pairing, that is g–motif. The interaction mode and full characterizations of g–motif will contribute to the study of the mismatched DNA interaction.

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