The T-Knot Motif Revisited

1999 ◽  
Vol 380 (10) ◽  
pp. 1247-1250 ◽  
Author(s):  
Fabio Polticelli ◽  
Stefano Pascarella ◽  
Domenico Bordo ◽  
Martino Bolognesi ◽  
Paolo Ascenzi
Keyword(s):  
Secondary Structure ◽  
Structural Feature ◽  
Three Dimensional ◽  
Structural Motif ◽  
Loop Length ◽  
Protein Chain ◽  
Hydrophobic Core ◽  
Biological Functions ◽  
Β Sheet

Abstract The T-knot scaffold, a disulphide-reinforced structural motif shared by several proteins with very different biological functions, has been defined as ‘a stretch of the protein chain which comprises two strands of a β-sheet and three loops, knotted by two disulphides into the shape of the letter T’. In this communication we show that the presence of a central β-sheet is not a required structural feature for proteins sharing the T-knot topology. Moreover, superposition of the three-dimensional structures of representative members of the T-knot family highlights a common and structurally well-defined core, formed by the two knotted disulphides, substituting for a larger residue-based hydrophobic core. These results suggest that folding and stability of the T-knot scaffold mainly depend on the geometry of the two knotted disulphides and on the loop length, and that the secondary structure elements are not a prerequisite for motif formation. Accordingly, a redefinition of the T-knot motif is proposed.

The CXXC motif: crystal structure of an active-site variant of Escherichia coli thioredoxin

1999 ◽  
Vol 55 (9) ◽  
pp. 1533-1538 ◽  
Author(s):  
L. Wayne Schultz ◽  
Peter T. Chivers ◽  
Ronald T. Raines
Keyword(s):  
Escherichia Coli ◽  
Active Site ◽  
Reduction Potential ◽  
Three Dimensional ◽  
Structural Motif ◽  
Dimensional Structure ◽  
Wild Type ◽  
C Protein ◽  
Protein Disulfide ◽  
Β Sheet

The 2.2 Å crystalline structure of an oxidized active-site variant of Escherichia coli thioredoxin (Trx) has been solved. Trx is a 12 kDa enzyme which catalyzes the oxidation of dithiols and the reduction and isomerization of disulfides in other proteins. Its active site contains the common structural motif CXXC. Protein-disulfide isomerase (PDI), a 57 kDa homolog of Trx, contains four Trx-like domains. The three-dimensional structure of PDI is unknown. PDI-deficient Saccharomyces cerevisiae are inviable. An active-site variant of Trx which complements PDI-deficient yeast has the active-site sequence Cys32-Val33-Trp34-Cys35 (CVWC). The reduction potential of oxidized CVWC Trx (E°′ = −0.230 V) is altered significantly from that of the wild-type enzyme (E°′ = −0.270 V). However, the structure of the oxidized CVWC enzyme is almost identical to that of wild-type Trx. The addition of valine and tryptophan in the active site is likely to increase the reduction potential, largely by decreasing the pKa of the Cys32 thiol in the reduced enzyme. Unlike in wild-type Trx, significant protein–protein contacts occur in the crystal. Protein molecules related by a crystallographic twofold axis form a dimer in the crystal. The dimer forms as an extension of the twisted mixed β-sheet which composes the backbone of each Trx structure.

Self-Assembled β-Sheet Architectures for Bone-Tissue Engineering

1999 ◽  
Vol 599 ◽  
Author(s):  
G. Spreitzer ◽  
J. Doctor ◽  
D. W. Wright
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Critical Role ◽  
Three Dimensional ◽  
Structural Motif ◽  
Synthetic Approach ◽  
Self Assembled ◽  
Β Sheet

AbstractAdvances in the understanding of biomineralization processes in a variety of organisms have revealed the critical role of three-dimensional scaffolding architectures to create a highly functionalized surface. These complex matrices function on a variety of length scales ranging from the macromolecular (10–100 nm) to the cellular (1–10mm) and larger. One dominant structural motif found in many of these architectures is macromolecules containing antiparallel β-pleated sheets. These “hints” from Nature have lead to the iterative design and development of a novel multipurpose platform technology based on a self-assembled periodic peptide architecture for use in bone-tissue engineering. Combining molecular modeling, structural biochemistry and synthetic techniques, we have produced a β-sheet hollow tube peptide nanoassembly. Such a synthetic approach allows for the template's designed parameters of electrostatic, geometric and stereochemical complimentarily to match those of the desired biomineral. Consequently, these templates readily nucleate calcite. Future studies will investigate the in vitro osteoconductive and osteogenic properties of these templates.

scholarly journals The Status of Edge Strands in Ferredoxin-Like Fold

Symmetry ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1032
Author(s):  
Mateusz Banach ◽  
Piotr Fabian ◽  
Katarzyna Stapor ◽  
Leszek Konieczny ◽  
Magdalena Ptak-Kaczor ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Hydrophobic Core ◽  
Current Analysis ◽  
Professional Literature ◽  
The Status ◽  
The Subject ◽  
Β Sheets ◽  
Β Sheet

There is an opinion in professional literature that edge-strands in β-sheet are critical to the processes of amyloid transformation. Propagation of fibrillar forms mainly takes place on the basis of β-sheet type interactions. In many proteins, the edge strands represent only a partially matched form to the β-sheet. Therefore, the edge-strand takes slightly distorted forms. The assessment of the level of arrangement can be carried out based on studying the secondary structure as well as the structure of the hydrophobic core. For this purpose, a fuzzy oil drop model was used to determine the contribution of each fragment with a specific secondary structure to the construction of the system being the effect of a certain synergy, which results in the construction of a hydrophobic core. Studying the participation of β-sheets edge fragments in the hydrophobic core construction is the subject of the current analysis. Statuses of these edge fragments in β-sheets in ferredoxin-like folds are treated as factors that disturb the symmetry of the system.

A method of predicting the secondary protein structure based on dictionaries

2015 ◽  
Vol 11 (3) ◽  
Author(s):  
Irena Roterman-Konieczna ◽  
Piotr Fabian ◽  
Katarzyna Stąpor
Keyword(s):  
Secondary Structure ◽  
Tertiary Structure ◽  
Three Dimensional ◽  
Shape Description ◽  
Protein Chain ◽  
Local Shape ◽  
3D Information ◽  
Secondary Protein Structure ◽  
Different Levels ◽  
Structural Code

AbstractThe shape of a protein chain may be analyzed at different levels of details. The ultimate shape description contains three-dimensional coordinates of all atoms in the chain. In many cases, a description of the local shape, namely secondary structure, is enough to determine some properties of proteins. Although obtaining the full three-dimensional (3D) information also defines the secondary structure, the problem of finding this precise 3D shape (tertiary structure) given only the amino acid sequence is very complex. However, the secondary structure may be found even without having the full 3D information. Many methods have been developed for this purpose. Most of them are based on similarities of the analyzed protein chain to other proteins that are already analyzed and have a known secondary structure. The presented paper proposes a method based on dictionaries of known structures for predicting the secondary structure from either the primary structure or the so-called structural code. Accuracies of up to 79% have been achieved.

scholarly journals In vivo aspects of protein folding and quality control

Science ◽  
2016 ◽  
Vol 353 (6294) ◽  
pp. aac4354 ◽  
Author(s):  
David Balchin ◽  
Manajit Hayer-Hartl ◽  
F. Ulrich Hartl
Keyword(s):  
Molecular Chaperones ◽  
Three Dimensional ◽  
Pharmacological Intervention ◽  
Folding Pathway ◽  
Protein Homeostasis ◽  
Protein Chain ◽  
Biological Functions ◽  
Integrated Network ◽  
Cellular Environment

Most proteins must fold into unique three-dimensional structures to perform their biological functions. In the crowded cellular environment, newly synthesized proteins are at risk of misfolding and forming toxic aggregate species. To ensure efficient folding, different classes of molecular chaperones receive the nascent protein chain emerging from the ribosome and guide it along a productive folding pathway. Because proteins are structurally dynamic, constant surveillance of the proteome by an integrated network of chaperones and protein degradation machineries is required to maintain protein homeostasis (proteostasis). The capacity of this proteostasis network declines during aging, facilitating neurodegeneration and other chronic diseases associated with protein aggregation. Understanding the proteostasis network holds the promise of identifying targets for pharmacological intervention in these pathologies.

Analysis and prediction of structural motifs in the glycolytic enzymes

1981 ◽  
Vol 293 (1063) ◽  
pp. 177-189 ◽  
Keyword(s):  
Amino Acid ◽  
Lactate Dehydrogenase ◽  
Secondary Structure ◽  
Amino Acid Sequence ◽  
Common Ancestor ◽  
Three Dimensional ◽  
Prediction Algorithm ◽  
General Rules ◽  
Pathway Diagrams ◽  
Β Sheet

Protein crystallography has determined the three-dimensional structures of 10 of the 13 enzymes of the glycolytic pathway. Diagrams and details of these enzyme structures are given in the paper. Most of the enzyme domains are variations and extensions of a many (4- 9)-stranded, predominantly or totally parallel, β-sheet that is shielded from solvent by α-helices (i.e. α/β structures). There are strong structural similarities between the domains of some, but not all, of the enzymes. In particular the dinucleotide binding fold of lactate dehydrogenase and the β-barrel of triose phosphate isomerase are found in other domains. General rules governing the topology and packing of α-helices against a β-sheet provide a basis for the combinatorial prediction of the tertiary fold of glycolytic domains from their amino acid sequence and observed secondary structure. The prediction algorithm demonstrates that there are severe restrictions on the number of possible structures. However, these restrictions do not fully explain some of the remarkable structural similarities between different enzymes that probably result from evolution from a common ancestor.

scholarly journals Structural relation matching: an algorithm to identify structural patterns into RNAs and their interactions

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michela Quadrini
Keyword(s):  
Hydrogen Bonding ◽  
Secondary Structure ◽  
Nucleotide Sequence ◽  
Thermus Thermophilus ◽  
Three Dimensional ◽  
Secondary Structures ◽  
Structural Effect ◽  
Biological Processes ◽  
Structural Pattern ◽  
Rna Molecules

Abstract RNA molecules play crucial roles in various biological processes. Their three-dimensional configurations determine the functions and, in turn, influences the interaction with other molecules. RNAs and their interaction structures, the so-called RNA–RNA interactions, can be abstracted in terms of secondary structures, i.e., a list of the nucleotide bases paired by hydrogen bonding within its nucleotide sequence. Each secondary structure, in turn, can be abstracted into cores and shadows. Both are determined by collapsing nucleotides and arcs properly. We formalize all of these abstractions as arc diagrams, whose arcs determine loops. A secondary structure, represented by an arc diagram, is pseudoknot-free if its arc diagram does not present any crossing among arcs otherwise, it is said pseudoknotted. In this study, we face the problem of identifying a given structural pattern into secondary structures or the associated cores or shadow of both RNAs and RNA–RNA interactions, characterized by arbitrary pseudoknots. These abstractions are mapped into a matrix, whose elements represent the relations among loops. Therefore, we face the problem of taking advantage of matrices and submatrices. The algorithms, implemented in Python, work in polynomial time. We test our approach on a set of 16S ribosomal RNAs with inhibitors of Thermus thermophilus, and we quantify the structural effect of the inhibitors.

scholarly journals Online biophysical predictions for SARS-CoV-2 proteins

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Luciano Kagami ◽  
Joel Roca-Martínez ◽  
Jose Gavaldá-García ◽  
Pathmanaban Ramasamy ◽  
K. Anton Feenstra ◽  
...  
Keyword(s):  
Protein Sequence ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Static Structure ◽  
Homologous Proteins ◽  
Structure Based Drug Design ◽  
Protein Protein Interaction ◽  
Link Type ◽  
Dynamics Simulations ◽  
Β Sheet

Abstract Background The SARS-CoV-2 virus, the causative agent of COVID-19, consists of an assembly of proteins that determine its infectious and immunological behavior, as well as its response to therapeutics. Major structural biology efforts on these proteins have already provided essential insights into the mode of action of the virus, as well as avenues for structure-based drug design. However, not all of the SARS-CoV-2 proteins, or regions thereof, have a well-defined three-dimensional structure, and as such might exhibit ambiguous, dynamic behaviour that is not evident from static structure representations, nor from molecular dynamics simulations using these structures. Main We present a website (https://bio2byte.be/sars2/) that provides protein sequence-based predictions of the backbone and side-chain dynamics and conformational propensities of these proteins, as well as derived early folding, disorder, β-sheet aggregation, protein-protein interaction and epitope propensities. These predictions attempt to capture the inherent biophysical propensities encoded in the sequence, rather than context-dependent behaviour such as the final folded state. In addition, we provide the biophysical variation that is observed in homologous proteins, which gives an indication of the limits of their functionally relevant biophysical behaviour. Conclusion The https://bio2byte.be/sars2/ website provides a range of protein sequence-based predictions for 27 SARS-CoV-2 proteins, enabling researchers to form hypotheses about their possible functional modes of action.

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