Lithium-Protein Interactions: Analysis of Lithium-Containing Protein Crystal Structures Deposited in the Protein Data Bank

2020 ◽  
Vol 27 (8) ◽  
pp. 763-769
Author(s):  
Oliviero Carugo
Keyword(s):  
Small Molecules ◽  
Crystal Structures ◽  
Protein Data Bank ◽  
Protein Interactions ◽  
Structural Information ◽  
Protein Complexes ◽  
Aerospace Industry ◽  
Data Bank ◽  
Protein Crystal ◽  
Side Chain

Background: Despite the fact that lithium is not a biologically essential metallic element, its pharmacological properties are well known and human exposure to lithium is increasingly possible because of its used in aerospace industry and in batteries. Objective: Lithium-protein interactions are therefore interesting and the surveys of the structures of lithium-protein complexes is described in this paper. Methods: A high quality non-redundant set of lithium containing protein crystal structures was extracted from the Protein Data Bank and the stereochemistry of the lithium first coordination sphere was examined in detail. Results: Four main observations were reported: (i) lithium interacts preferably with oxygen atoms; (ii) preferably with side-chain atoms; (iii) preferably with Asp or Glu carboxylates; (iv) the coordination number tends to be four with stereochemical parameters similar to those observed in small molecules containing lithium. Conclusion: Although structural information on lithium-protein, available from the Protein Data Bank, is relatively scarce, these trends appears to be so clear that one may suppose that they will be confirmed by further data that will join the Protein Data Bank in the future.

scholarly journals Conformation-dependent restraints for polynucleotides: the sugar moiety

2019 ◽  
Vol 48 (2) ◽  
pp. 962-973
Author(s):  
Marcin Kowiel ◽  
Dariusz Brzezinski ◽  
Miroslaw Gilski ◽  
Mariusz Jaskolski
Keyword(s):  
Nucleic Acids ◽  
Crystal Structures ◽  
Protein Data Bank ◽  
Data Bank ◽  
Experimental Methods ◽  
Side Chain ◽  
Torsion Angles ◽  
Sugar Moiety ◽  
Structural Database ◽  
Different Parts

Abstract Stereochemical restraints are commonly used to aid the refinement of macromolecular structures obtained by experimental methods at lower resolution. The standard restraint library for nucleic acids has not been updated for over two decades and needs revision. In this paper, geometrical restraints for nucleic acids sugars are derived using information from high-resolution crystal structures in the Cambridge Structural Database. In contrast to the existing restraints, this work shows that different parts of the sugar moiety form groups of covalent geometry dependent on various chemical and conformational factors, such as the type of ribose or the attached nucleobase, and ring puckering or rotamers of the glycosidic (χ) or side-chain (γ) torsion angles. Moreover, the geometry of the glycosidic link and the endocyclic ribose bond angles are functionally dependent on χ and sugar pucker amplitude (τm), respectively. The proposed restraints have been positively validated against data from the Nucleic Acid Database, compared with an ultrahigh-resolution Z-DNA structure in the Protein Data Bank, and tested by re-refining hundreds of crystal structures in the Protein Data Bank. The conformation-dependent sugar restraints presented in this work are publicly available in REFMAC, PHENIX and SHELXL format through a dedicated RestraintLib web server with an API function.

scholarly journals Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin

2015 ◽  
Vol 71 (9) ◽  
pp. 1965-1979 ◽  
Author(s):  
Ivan Shabalin ◽  
Zbigniew Dauter ◽  
Mariusz Jaskolski ◽  
Wladek Minor ◽  
Alexander Wlodawer
Keyword(s):  
Side Effects ◽  
Data Collection ◽  
Anticancer Activity ◽  
Crystal Structures ◽  
Protein Data Bank ◽  
Diffraction Data ◽  
Chemical Nature ◽  
Protein Complexes ◽  
Data Bank ◽  
Cautionary Tale

The anticancer activity of platinum-containing drugs such as cisplatin and carboplatin is considered to primarily arise from their interactions with nucleic acids; nevertheless, these drugs, or the products of their hydrolysis, also bind to proteins, potentially leading to the known side effects of the treatments. Here, over 40 crystal structures deposited in the Protein Data Bank (PDB) of cisplatin and carboplatin complexes of several proteins were analysed. Significant problems of either a crystallographic or a chemical nature were found in most of the presented atomic models and they could be traced to less or more serious deficiencies in the data-collection and refinement procedures. The re-evaluation of these data and models was possible thanks to their mandatory or voluntary deposition in publicly available databases, emphasizing the point that the availability of such data is critical for making structural science reproducible. Based on this analysis of a selected group of macromolecular structures, the importance of deposition of raw diffraction data is stressed and a procedure for depositing, tracking and using re-refined crystallographic models is suggested.

scholarly journals Naked Metal Cations Swimming in Protein Crystals

Crystals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 581
Author(s):  
Kristina Djinović-Carugo ◽  
Oliviero Carugo
Keyword(s):  
Crystal Structures ◽  
Protein Data Bank ◽  
Metal Cations ◽  
Data Bank ◽  
Protein Crystal ◽  
Protein Crystals ◽  
Systematic Survey

The presence of isolated metal cations, far from any other atom, is not uncommon in protein crystal structures. A systematic survey of the Protein Data Bank showed that nearly 8% of the metal cations are naked, more frequently if they can interact only electrostatically with their neighbors. Surprisingly, this seemed to be only weakly related to the crystallographic resolution.

Protein Interaction Domains and Post-Translational Modifications: Structural Features and Drug Discovery Applications

2020 ◽  
Vol 27 (37) ◽  
pp. 6306-6355 ◽  
Author(s):  
Marian Vincenzi ◽  
Flavia Anna Mercurio ◽  
Marilisa Leone
Keyword(s):  
Drug Discovery ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Structural Information ◽  
Protein Complexes ◽  
Structural Features ◽  
Protein Protein Interactions ◽  
Modular Architecture ◽  
Post Translational Modifications ◽  
Interaction Domains

Background:: Many pathways regarding healthy cells and/or linked to diseases onset and progression depend on large assemblies including multi-protein complexes. Protein-protein interactions may occur through a vast array of modules known as protein interaction domains (PIDs). Objective:: This review concerns with PIDs recognizing post-translationally modified peptide sequences and intends to provide the scientific community with state of art knowledge on their 3D structures, binding topologies and potential applications in the drug discovery field. Method:: Several databases, such as the Pfam (Protein family), the SMART (Simple Modular Architecture Research Tool) and the PDB (Protein Data Bank), were searched to look for different domain families and gain structural information on protein complexes in which particular PIDs are involved. Recent literature on PIDs and related drug discovery campaigns was retrieved through Pubmed and analyzed. Results and Conclusion:: PIDs are rather versatile as concerning their binding preferences. Many of them recognize specifically only determined amino acid stretches with post-translational modifications, a few others are able to interact with several post-translationally modified sequences or with unmodified ones. Many PIDs can be linked to different diseases including cancer. The tremendous amount of available structural data led to the structure-based design of several molecules targeting protein-protein interactions mediated by PIDs, including peptides, peptidomimetics and small compounds. More studies are needed to fully role out, among different families, PIDs that can be considered reliable therapeutic targets, however, attacking PIDs rather than catalytic domains of a particular protein may represent a route to obtain selective inhibitors.

scholarly journals Validation and correction of Zn–Cys x His y complexes

2016 ◽  
Vol 72 (10) ◽  
pp. 1110-1118 ◽  
Author(s):  
Wouter G. Touw ◽  
Bart van Beusekom ◽  
Jochem M. G. Evers ◽  
Gert Vriend ◽  
Robbie P. Joosten
Keyword(s):  
Crystal Structures ◽  
Protein Data Bank ◽  
Model Validation ◽  
Data Bank ◽  
Zinc Complexes ◽  
Zinc Ions ◽  
Tetrahedral Complex ◽  
Context Sensitive

Many crystal structures in the Protein Data Bank contain zinc ions in a geometrically distorted tetrahedral complex with four Cys and/or His ligands. A method is presented to automatically validate and correct these zinc complexes. Analysis of the corrected zinc complexes shows that the average Zn–Cys distances and Cys–Zn–Cys angles are a function of the number of cysteines and histidines involved. The observed trends can be used to develop more context-sensitive targets for model validation and refinement.

scholarly journals IMAAAGINE: a webserver for searching hypothetical 3D amino acid side chain arrangements in the Protein Data Bank

2013 ◽  
Vol 41 (W1) ◽  
pp. W432-W440 ◽  
Author(s):  
Nurul Nadzirin ◽  
Peter Willett ◽  
Peter J. Artymiuk ◽  
Mohd Firdaus-Raih
Keyword(s):  
Amino Acid ◽  
Protein Data Bank ◽  
Data Bank ◽  
Side Chain ◽  
Amino Acid Side Chain

THE RAMACHANDRAN MAP OF MORE THAN 6,500 PERFECT POLYPEPTIDE CHAINS

2007 ◽  
Vol 02 (03n04) ◽  
pp. 267-271
Author(s):  
ZOLTÁN SZABADKA ◽  
RAFAEL ÖRDÖG ◽  
VINCE GROLMUSZ
Keyword(s):  
Protein Data Bank ◽  
Structural Information ◽  
Data Bank ◽  
Ramachandran Map ◽  
Tenfold Increase ◽  
Automated Processing ◽  
Data Points ◽  
Α Helix ◽  
The Right ◽  
Polypeptide Chains

The Protein Data Bank (PDB) is the most important depository of protein structural information, containing more than 45,000 deposited entries today. Because of its inhomogeneous structure, its fully automated processing is almost impossible. In a previous work, we cleaned and re-structured the entries in the Protein Data Bank, and from the result we have built the RS-PDB database. Using the RS-PDB database, we draw a Ramachandran-plot from 6,593 "perfect" polypeptide chains found in the PDB, containing 1,192,689 residues. This is a more than tenfold increase in the size of data analyzed before this work. The density of the data points makes it possible to draw a logarithmic heat map enhanced Ramachandran map, showing the fine inner structure of the right-handed α-helix region.

Use of Patterson-based methods automatically to determine the structures of heavy-atom-containing proteins with up to 6000 non-hydrogen atoms in the asymmetric unit

2006 ◽  
Vol 39 (5) ◽  
pp. 728-734 ◽  
Author(s):  
Maria Cristina Burla ◽  
Rocco Caliandro ◽  
Benedetta Carrozzini ◽  
Giovanni Luca Cascarano ◽  
Liberato De Caro ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Protein Data Bank ◽  
Heavy Atom ◽  
Data Bank ◽  
Atomic Resolution ◽  
Asymmetric Unit ◽  
Hydrogen Atoms ◽  
Heavy Atoms ◽  
Density Maps ◽  
Resolution Data

The Patterson superposition methods described by Burlaet al.[J. Appl. Cryst.(2006),39, 527–535], based on the use of the `multiple implication functions', have been enriched by supplementary filtering techniques based on some general (resolution-dependent) features of both the Patterson and the electron density maps. The method has been implemented in a modified version of the programSIR2004and tested using a set of 20 crystal structures selected from the Protein Data Bank, having a number of non-hydrogen atoms in the asymmetric unit larger than 2000, atomic resolution data and some heavy atoms (equal to or heavier than Ca). The new phasing procedure is able to solve most of the test structures, among which there are two proteins with more than 6000 non-hydrogen atoms in the asymmetric unit, so extending by far the complexity today commonly considered as the limit for Patterson-based methods (i.e.about 2000 non-hydrogen atoms).

Synchrotron radiation circular dichroism (SRCD) spectroscopy: an enhanced method for examining protein conformations and protein interactions

2010 ◽  
Vol 38 (4) ◽  
pp. 861-873 ◽  
Author(s):  
B.A. Wallace ◽  
Robert W. Janes
Keyword(s):  
Circular Dichroism ◽  
Synchrotron Radiation ◽  
Protein Interactions ◽  
Structural Information ◽  
Data Bank ◽  
Cd Spectroscopy ◽  
Circular Dichroism Spectroscopy ◽  
Protein Conformations ◽  
Mutant Proteins ◽  
Circular Dichroïsm

CD (circular dichroism) spectroscopy is a well-established technique in structural biology. SRCD (synchrotron radiation circular dichroism) spectroscopy extends the utility and applications of conventional CD spectroscopy (using laboratory-based instruments) because the high flux of a synchrotron enables collection of data at lower wavelengths (resulting in higher information content), detection of spectra with higher signal-to-noise levels and measurements in the presence of absorbing components (buffers, salts, lipids and detergents). SRCD spectroscopy can provide important static and dynamic structural information on proteins in solution, including secondary structures of intact proteins and their domains, protein stability, the differences between wild-type and mutant proteins, the identification of natively disordered regions in proteins, and the dynamic processes of protein folding and membrane insertion and the kinetics of enzyme reactions. It has also been used to effectively study protein interactions, including protein–protein complex formation involving either induced-fit or rigid-body mechanisms, and protein–lipid complexes. A new web-based bioinformatics resource, the Protein Circular Dichroism Data Bank (PCDDB), has been created which enables archiving, access and analyses of CD and SRCD spectra and supporting metadata, now making this information publicly available. To summarize, the developing method of SRCD spectroscopy has the potential for playing an important role in new types of studies of protein conformations and their complexes.

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