Conservation of Amino Acids into Multiple Alignments Involved in Pairwise Interactions in Three-Dimensional Protein Structures

2003 ◽  
Vol 01 (03) ◽  
pp. 505-520 ◽  
Author(s):  
Mounir Errami ◽  
Christophe Geourjon ◽  
Gilbert Deléage
Keyword(s):  
Amino Acids ◽  
Disulfide Bonds ◽  
Hydrophobic Interactions ◽  
Protein Structures ◽  
Three Dimensional ◽  
Structural Features ◽  
Multiple Alignment ◽  
Salt Bridges ◽  
Multiple Alignments ◽  
Multiple Sequences

We present an original strategy, that involves a bioinformatic software structure, in order to perform an exhaustive and objective statistical analysis of three-dimensional structures of proteins. We establish the relationship between multiple sequences alignments and various structural features of proteins. We show that amino acids implied in disulfide bonds, salt bridges and hydrophobic interactions are particularly conserved. Effects of identity, global similarity within alignments, and accessibility of interactions have been studied. Furthermore, we point out that the more variable the sequences within a multiple alignment, the more informative the multiple alignment. The results support multiple alignments usefulness for predictions of structural features.

Different rates of formation of secondary and tertiary structure during renaturation of urea-denatured human serum albumin

1989 ◽  
Vol 54 (9) ◽  
pp. 2542-2549 ◽  
Author(s):  
Josef Chmelík
Keyword(s):  
Protein Folding ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Disulfide Bonds ◽  
Tertiary Structure ◽  
Hydrophobic Interactions ◽  
Protein Structures ◽  
Three Dimensional ◽  
Comparison Of The Results

A comparison of the results of our polarimetric measurements with the polarographic experiments reported earlier shows that the restoration of the secondary structure during the renaturation of human serum albumin is a process which is faster than the formation of the tertiary structure. These results, which are in agreement with the data on the kinetic control of protein folding, are discussed from the viewpoint of the importance of the individual types of interactions which take place during the formation and stabilization of three-dimensional protein structures. We have been able to demonstrate the great importance of electrostatic and hydrophobic interactions which together with the disulfide bonds are essential for the reversibility of the denaturation phenomena. The discussion also shows the essential role which evolution processes play in the selection of the mode of protein folding.

PREDICTION OF THE THREE-DIMENSIONAL STRUCTURE OF THE ENZYMATIC PART OF T-PA

1987 ◽  
Author(s):  
A Heckel ◽  
K M Hasselbach
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Active Site ◽  
Serine Proteases ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
Salt Bridges ◽  
Three Dimensional Structure ◽  
Insertions And Deletions

Up to now the three-dimensional structure of t-PA or parts of this enzyme is unknown. Using computer graphical methods the spatial structure of the enzymatic part of t-PA is predicted on the hypothesis, the three-dimensional backbone structure of t-PA being similar to that of other serine proteases. The t-PA model was built up in three steps:1) Alignment of the t-PA sequence with other serine proteases. Comparison of enzyme structures available from Brookhaven Protein Data Bank proved elastase as a basis for modeling.2) Exchange of amino acids of elastase differing from the t-PA sequence. The replacement of amino acids was performed such that backbone atoms overlapp completely and side chains superpose as far as possible.3) Modeling of insertions and deletions. To determine the spatial arrangement of insertions and deletions parts of related enzymes such as chymotrypsin or trypsin were used whenever possible. Otherwise additional amino acid sequences were folded to a B-turn at the surface of the proteine, where all insertions or deletions are located. Finally the side chain torsion angles of amino acids were optimised to prevent close contacts of neigh bouring atoms and to improve hydrogen bonds and salt bridges.The resulting model was used to explain binding of arginine 560 of plasminogen to the active site of t-PA. Arginine 560 interacts with Asp 189, Gly 19 3, Ser 19 5 and Ser 214 of t-PA (chymotrypsin numbering). Furthermore interaction of chromo-genic substrate S 2288 with the active site of t-PA was studied. The need for D-configuration of the hydrophobic amino acid at the N-terminus of this tripeptide derivative could be easily explained.

scholarly journals Unusual quaternary structure of a homodimeric synergistic-type toxin from mamba snake venom defines its molecular evolution

2020 ◽  
Vol 477 (20) ◽  
pp. 3951-3962
Author(s):  
Narumi Aoki-Shioi ◽  
Chacko Jobichen ◽  
J. Sivaraman ◽  
R. Manjunatha Kini
Keyword(s):  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Quaternary Structure ◽  
Hydrophobic Interactions ◽  
Biological Effects ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Common Structure

Snake venoms are complex mixtures of enzymes and nonenzymatic proteins that have evolved to immobilize and kill prey animals or deter predators. Among them, three-finger toxins (3FTxs) belong to the largest superfamily of nonenzymatic proteins. They share a common structure of three β-stranded loops extending like fingers from a central core containing all four conserved disulfide bonds. Most 3FTxs are monomers and through subtle changes in their amino acid sequences, they interact with different receptors, ion channels and enzymes to exhibit a wide variety of biological effects. The 3FTxs have further expanded their pharmacological space through covalent or noncovalent dimerization. Synergistic-type toxins (SynTxs) isolated from the deadly mamba venoms, although nontoxic, have been known to enhance the toxicity of other venom proteins. However, the details of three-dimensional structure and molecular mechanism of activity of this unusual class of 3FTxs are unclear. We determined the first three-dimensional structure of a SynTx isolated from Dendroaspis jamesoni jamesoni (Jameson's mamba) venom. The SynTx forms a unique homodimer that is held together by an interchain disulfide bond. The dimeric interface is elaborate and encompasses loops II and III. In addition to the inter-subunit disulfide bond, the hydrogen bonds and hydrophobic interactions between the monomers contribute to the dimer formation. Besides, two sulfate ions that mediate interactions between the monomers. This unique quaternary structure is evolved through noncovalent homodimers such as κ-bungarotoxins. This novel dimerization further enhances the diversity in structure and function of 3FTxs.

scholarly journals Defining the familial fold of the vicilin-buried peptide family

2020 ◽  
Author(s):  
Colton D. Payne ◽  
Grishma Vadlamani ◽  
Mark F. Fisher ◽  
Jingjing Zhang ◽  
Richard J. Clark ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Seed Storage ◽  
Structural Features ◽  
Salt Bridges ◽  
Plant Seed ◽  
Helix Loop Helix ◽  
New Family ◽  
Helical Hairpin

ABSTRACTPlants and their seeds have been shown to be a rich source of cystine-stabilized peptides. Recently a new family of plant seed peptides whose sequences are buried within precursors for seed storage vicilins was identified. Members of this Vicilin Buried Peptide (VBP) family are found in distantly related plant species including the monocot date palm, as well as dicotyledonous species like pumpkin and sesame. Genetic evidence for their widespread occurrence indicates that they are of ancient origin. Limited structural studies have been conducted on VBP family members, but two members have been shown to adopt a helical hairpin fold. We here present an extensive characterization of VBPs using solution NMR spectroscopy, to better understand their structural features. Four peptides were produced by solid phase peptide synthesis and shown to adopt a helix-loop-helix hairpin fold, as a result of the I-IV/II-III ladder-like connectivity of their disulfide bonds. Inter-helix interactions, including hydrophobic contacts and salt bridges, are critical for the fold stability and control the angle at which the anti-parallel α-helices interface. Activities reported for VBPs include trypsin inhibitory activity and inhibition of ribosomal function, however their diverse structural features despite a common fold suggest additional bioactivities yet to be revealed are likely.

scholarly journals Structure-Function Relationships of Glucansucrase and Fructansucrase Enzymes from Lactic Acid Bacteria

2006 ◽  
Vol 70 (1) ◽  
pp. 157-176 ◽  
Author(s):  
Sacha A. F. T. van Hijum ◽  
Slavko Kralj ◽  
Lukasz K. Ozimek ◽  
Lubbert Dijkhuizen ◽  
Ineke G. H. van Geel-Schutten
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Molecular Mass ◽  
Catalytic Domain ◽  
Structural Information ◽  
Protein Structures ◽  
Three Dimensional ◽  
Structural Features ◽  
Product Specificity ◽  
Gram Positive Bacteria

SUMMARY Lactic acid bacteria (LAB) employ sucrase-type enzymes to convert sucrose into homopolysaccharides consisting of either glucosyl units (glucans) or fructosyl units (fructans). The enzymes involved are labeled glucansucrases (GS) and fructansucrases (FS), respectively. The available molecular, biochemical, and structural information on sucrase genes and enzymes from various LAB and their fructan and α-glucan products is reviewed. The GS and FS enzymes are both glycoside hydrolase enzymes that act on the same substrate (sucrose) and catalyze (retaining) transglycosylation reactions that result in polysaccharide formation, but they possess completely different protein structures. GS enzymes (family GH70) are large multidomain proteins that occur exclusively in LAB. Their catalytic domain displays clear secondary-structure similarity with α-amylase enzymes (family GH13), with a predicted permuted (β/α)8 barrel structure for which detailed structural and mechanistic information is available. Emphasis now is on identification of residues and regions important for GS enzyme activity and product specificity (synthesis of α-glucans differing in glycosidic linkage type, degree and type of branching, glucan molecular mass, and solubility). FS enzymes (family GH68) occur in both gram-negative and gram-positive bacteria and synthesize β-fructan polymers with either β-(2→6) (inulin) or β-(2→1) (levan) glycosidic bonds. Recently, the first high-resolution three-dimensional structures have become available for FS (levansucrase) proteins, revealing a rare five-bladed β-propeller structure with a deep, negatively charged central pocket. Although these structures have provided detailed mechanistic insights, the structural features in FS enzymes dictating the synthesis of either β-(2→6) or β-(2→1) linkages, degree and type of branching, and fructan molecular mass remain to be identified.

scholarly journals Membrane Topological Model of Glycosyltransferases of the GT-C Superfamily

2019 ◽  
Vol 20 (19) ◽  
pp. 4842 ◽  
Author(s):  
Andreia Albuquerque-Wendt ◽  
Hermann J. Hütte ◽  
Falk F. R. Buettner ◽  
Françoise H. Routier ◽  
Hans Bakker
Keyword(s):  
Amino Acids ◽  
Endoplasmic Reticulum ◽  
Multiple Alignment ◽  
Membrane Topology ◽  
Family Structures ◽  
Multiple Alignments ◽  
High Conservation ◽  
Topology Model ◽  
Membrane Spanning ◽  
Conserved Amino Acids

Glycosyltransferases that use polyisoprenol-linked donor substrates are categorized in the GT-C superfamily. In eukaryotes, they act in the endoplasmic reticulum (ER) lumen and are involved in N-glycosylation, glypiation, O-mannosylation, and C-mannosylation of proteins. We generated a membrane topology model of C-mannosyltransferases (DPY19 family) that concurred perfectly with the 13 transmembrane domains (TMDs) observed in oligosaccharyltransferases (STT3 family) structures. A multiple alignment of family members from diverse organisms highlighted the presence of only a few conserved amino acids between DPY19s and STT3s. Most of these residues were shown to be essential for DPY19 function and are positioned in luminal loops that showed high conservation within the DPY19 family. Multiple alignments of other eukaryotic GT-C families underlined the presence of similar conserved motifs in luminal loops, in all enzymes of the superfamily. Most GT-C enzymes are proposed to have an uneven number of TDMs with 11 (POMT, TMTC, ALG9, ALG12, PIGB, PIGV, and PIGZ) or 13 (DPY19, STT3, and ALG10) membrane-spanning helices. In contrast, PIGM, ALG3, ALG6, and ALG8 have 12 or 14 TMDs and display a C-terminal dilysine ER-retrieval motif oriented towards the cytoplasm. We propose that all members of the GT-C superfamily are evolutionary related enzymes with preserved membrane topology.

scholarly journals Liquid metal-tailored gluten network for protein-based e-skin

2021 ◽  
Author(s):  
Bin Chen ◽  
Yudong Cao ◽  
Zhuo Yan ◽  
Rui Liu ◽  
Yunjiao Zhao ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Disulfide Bonds ◽  
Protein Structures ◽  
Three Dimensional ◽  
Driving Mechanism ◽  
Self Healing ◽  
Structure Rearrangement ◽  
Electronic Skin ◽  
Regulation Method ◽  
Human Motions

Abstract Designing electronic skin (e-skin) with proteins is a critical way to endow e-skin with biocompatibility, but engineering protein structures to achieve controllable mechanical properties and self-healing ability remains a challenge. Here, we develop a hybrid gluten network through the incorporation of an eutectic gallium indium alloy (EGaIn) to design a self-healable e-skin with improved mechanical properties. The intrinsic reversible disulfide bonds/sulfhydryl groups reconfiguration of gluten networks is explored as a driving mechanism to introduce EGaIn as chemical cross-linkers to create hierarchical sulphur bonds, thus inducing the secondary structure rearrangement of gluten to form additional β-sheets as physical cross-linkers. Remarkably, this strategy allows the gluten network to realize a synthetic material-like stretchability (>1600%) and to endure a three-dimensional strain change. The obtained e-skin is biocompatible and biodegradable, and can sense strain changes from different scale human motions. The protein network micro-regulation method paves the way for future skin-like protein-based e-skin.

scholarly journals Structural features responsible for kinetic thermal stability of a carboxypeptidase from the archaebacterium Sulfolobus solfataricus

1993 ◽  
Vol 295 (3) ◽  
pp. 827-831 ◽  
Author(s):  
A Villa ◽  
L Zecca ◽  
P Fusi ◽  
S Colombo ◽  
G Tedeschi ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Thermal Inactivation ◽  
Metal Removal ◽  
Hydrophobic Interactions ◽  
Sulfolobus Solfataricus ◽  
Structural Features ◽  
Inactivation Rate ◽  
Salt Bridges ◽  
Native Conformation ◽  
Thermal Stability Of

Investigations were performed on the structural features responsible for kinetic thermal stability of a thermostable carboxypeptidase from the thermoacidophilic archaebacterium Sulfolobus solfataricus which had been purified previously and identified as a zinc metalloprotease [Colombo, D'Auria, Fusi, Zecca, Raia and Tortora (1992) Eur. J. Biochem. 206, 349-357]. Removal of Zn2+ by dialysis led to reversible activity loss, which was promptly restored by addition of 80 microM ZnCl2 to the assay mixture. For the first-order irreversible thermal inactivation the metal-depleted enzyme showed an activation energy value of 205.6 kJ.mol-1, which is considerably lower than that of the holoenzyme (494.4 kJ.mol-1). The values of activation free energies, enthalpies and entropies also dropped with metal removal. Thermal inactivation of the apoenzyme was very quick at 80 degrees C, whereas the holoenzyme was stable at the same temperature. These findings suggest a major stabilizing role for the bivalent cation. Chaotropic salts strongly destabilized the holoenzyme, showing that hydrophobic interactions are involved in maintaining the native conformation of the enzyme. However, the inactivation rate was also increased by sodium sulphate, acetate and chloride, which are not chaotropes, indicating that one or more salt bridges concur in stabilizing the active enzyme. Furthermore, at the extremes of the pH-stability curve, NaCl did not affect the inactivation rate, confirming the stabilizing role of intramolecular ionic bonds, as a pH-dependent decrease in stability is likely to occur from breaking of salt bridges involved in maintaining the native conformation of the protein.

scholarly journals Protein Three-Dimensional Structural Databases: Domains, Structurally Aligned Homologues and Superfamilies

1998 ◽  
Vol 54 (6) ◽  
pp. 1168-1177 ◽  
Author(s):  
R. Sowdhamini ◽  
David F. Burke ◽  
Charlotte Deane ◽  
Jing-fei Huang ◽  
Kenji Mizuguchi ◽  
...  
Keyword(s):  
World Wide Web ◽  
World Wide ◽  
Protein Structures ◽  
Three Dimensional ◽  
Structural Features ◽  
Graphical Interface ◽  
Sequence Alignments ◽  
Homologous Proteins ◽  
Structural Domains ◽  
The World

This paper reports the availability of a database of protein structural domains (DDBASE), an alignment database of homologous proteins (HOMSTRAD) and a database of structurally aligned superfamilies (CAMPASS) on the World Wide Web (WWW). DDBASE contains information on the organization of structural domains and their boundaries; it includes only one representative domain from each of the homologous families. This database has been derived by identifying the presence of structural domains in proteins on the basis of inter-secondary structural distances using the programDIAL[Sowdhamini & Blundell (1995),Protein Sci.4, 506–520]. The alignment of proteins in superfamilies has been performed on the basis of the structural features and relationships of individual residues using the programCOMPARER[Sali & Blundell (1990),J. Mol. Biol.212, 403–428]. The alignment databases contain information on the conserved structural features in homologous proteins and those belonging to superfamilies. Available data include the sequence alignments in structure-annotated formats and the provision for viewing superposed structures of proteins using a graphical interface. Such information, which is freely accessible on the WWW, should be of value to crystallographers in the comparison of newly determined protein structures with previously identified protein domains or existing families.

Mutational studies of protein structures and their stabilities

1992 ◽  
Vol 25 (2) ◽  
pp. 205-250 ◽  
Author(s):  
David Shortle
Keyword(s):  
Amino Acid ◽  
Functional Role ◽  
Hydrophobic Interactions ◽  
Protein Structures ◽  
Three Dimensional ◽  
Rnase A ◽  
Side Chain ◽  
Amino Acid Side Chain ◽  
X Ray Crystallography ◽  
And Function

The fundamental relationship between structure and function has served to guide investigations into the workings of living systems at all levels - from the whole organism to individual cells on down to individual molecules. When X-ray crystallography began to reveal the three-dimensional structures of proteins like myoglobin, lysozyme and RNase A, protein chemists were well prepared to draw inferences about functional mechanisms from the precise positioning of amino acid residues they could see. The close proximity between an amino acid side chain and a chemical group on a bound ligand strongly suggests a functional role for that side chain in binding affinity and specificity. Likewise, the nearly universal finding of large clusters of hydrophobic side chains buried in the core of proteins strongly supports a major functional role of hydrophobic interactions in protein folding and stability. Even though eminently plausible hypotheses like these, grounded in the most fundamental principles of chemistry and the logic of structure–function relationships, become widely accepted and make their way into textbooks, protein chemists have felt compelled to search for ways to test them and put them on a more quantitative basis.

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