scholarly journals Structure of Looped Regions in β-α- and α-β-Arches in Abcd-Units of Globular Proteins

2016 ◽  
Vol 11 (2) ◽  
pp. 159-169
Author(s):  
Е.В. Бражников ◽  
E.V. Brazhnikov
Keyword(s):  
Amino Acid ◽  
De Novo ◽  
Protein Structures ◽  
Three Dimensional ◽  
Structural Motif ◽  
Dimensional Structure ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Reverse Turn ◽  
Structure Of Proteins

Conformations of about 600 looped regions (loops) in β-α- and α-β-arches of a structural motif occurring in the abCd-unit of proteins were analyzed. On the whole, 258 abCd-units with a reverse turn of the polypeptide chain (236 PDB files) and 69 abCd-units with a direct turn (65 PDB files) were selected in non-homologous proteins. Four types of arches were studied: β-α- and α-β-ones at a direct turn of the chain; β-α- and α-β-ones at a reverse turn of the chain. For each type of arches, frequencies of loops occurrence of different lengths were determined and corresponding histograms were plotted. It was found that abCd-units with loops up to three amino acid residues long occur most frequently (57 %). In β-α-arches with a direct turn of the chain, loops consisting of two amino acid residues occur most often (44 %) and in 86% cases they have the βmαβαn - conformation. They have no Gly and Pro residues, and in position β there is an Asn residue. In such type of arches, the loops of one residue (βmεαn- or βmαLαn- conformation) contain the Gly residue most frequently. α-β-Arches with a direct turn of the chain have most commonly (18 %) loops of four amino acid residues. In this case, there is no predominant conformation of the loops. In β-α-arches with a reverse turn of the chain, most common are loops of seven amino acid residues (17%), and most part of them (88 %) have the βmαLββααββαn - conformation. α-β-Arches with a reverse turn of the chain contain most frequently (32%) loops of one amino acid residue (all Gly ones) with arch conformations αmεβn or αmαLβn. The above structural analysis of the abCd-unit has useful information for prediction of the three-dimensional structure of proteins and for molecular simulation of the de novo design of protein structures.

Characteristics of Two Forms of α-Amylases and Structural Implication

1999 ◽  
Vol 65 (10) ◽  
pp. 4652-4658 ◽  
Author(s):  
Kohji Ohdan ◽  
Takashi Kuriki ◽  
Hiroki Kaneko ◽  
Jiro Shimada ◽  
Toshikazu Takada ◽  
...  
Keyword(s):  
Amino Acid ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
Amino Acid Residues ◽  
Amylase Gene ◽  
Raw Starch ◽  
Raw Starch Binding ◽  
Terminal Amino ◽  
Carboxyl Terminal

ABSTRACT Complete (Ba-L) and truncated (Ba-S) forms of α-amylases fromBacillus subtilis X-23 were purified, and the amino- and carboxyl-terminal amino acid sequences of Ba-L and Ba-S were determined. The amino acid sequence deduced from the nucleotide sequence of the α-amylase gene indicated that Ba-S was produced from Ba-L by truncation of the 186 amino acid residues at the carboxyl-terminal region. The results of genomic Southern analysis and Western analysis suggested that the two enzymes originated from the same α-amylase gene and that truncation of Ba-L to Ba-S occurred during the cultivation of B. subtilis X-23 cells. Although the primary structure of Ba-S was approximately 28% shorter than that of Ba-L, the two enzyme forms had the same enzymatic characteristics (molar catalytic activity, amylolytic pattern, transglycosylation ability, effect of pH on stability and activity, optimum temperature, and raw starch-binding ability), except that the thermal stability of Ba-S was higher than that of Ba-L. An analysis of the secondary structure as well as the predicted three-dimensional structure of Ba-S showed that Ba-S retained all of the necessary domains (domains A, B, and C) which were most likely to be required for functionality as α-amylase.

scholarly journals Insights into the quaternary association of proteins through structure graphs: a case study of lectins

2005 ◽  
Vol 391 (1) ◽  
pp. 1-15 ◽  
Author(s):  
K. V. Brinda ◽  
Avadhesha Surolia ◽  
Sarawathi Vishveshwara
Keyword(s):  
Amino Acid ◽  
Protein Structures ◽  
Present Review ◽  
Dimensional Structure ◽  
Protein Oligomerization ◽  
Amino Acid Residues ◽  
Sequence Motifs ◽  
Structural Determinants ◽  
Legume Lectin ◽  
Quaternary Structures

The unique three-dimensional structure of both monomeric and oligomeric proteins is encoded in their sequence. The biological functions of proteins are dependent on their tertiary and quaternary structures, and hence it is important to understand the determinants of quaternary association in proteins. Although a large number of investigations have been carried out in this direction, the underlying principles of protein oligomerization are yet to be completely understood. Recently, new insights into this problem have been gained from the analysis of structure graphs of proteins belonging to the legume lectin family. The legume lectins are an interesting family of proteins with very similar tertiary structures but varied quaternary structures. Hence they have become a very good model with which to analyse the role of primary structures in determining the modes of quaternary association. The present review summarizes the results of a legume lectin study as well as those obtained from a similar analysis carried out here on the animal lectins, namely galectins, pentraxins, calnexin, calreticulin and rhesus rotavirus Vp4 sialic-acid-binding domain. The lectin structure graphs have been used to obtain clusters of non-covalently interacting amino acid residues at the intersubunit interfaces. The present study, performed along with traditional sequence alignment methods, has provided the signature sequence motifs for different kinds of quaternary association seen in lectins. Furthermore, the network representation of the lectin oligomers has enabled us to detect the residues which make extensive interactions (‘hubs’) across the oligomeric interfaces that can be targetted for interface-destabilizing mutations. The present review also provides an overview of the methodology involved in representing oligomeric protein structures as connected networks of amino acid residues. Further, it illustrates the potential of such a representation in elucidating the structural determinants of protein–protein association in general and will be of significance to protein chemists and structural biologists.

Location of amino acid residues important for cobra venom factor function mapped on the three-dimensional structure of complement components C3 and C3c

2007 ◽  
Vol 44 (1-3) ◽  
pp. 172 ◽  
Author(s):  
David C. Fritzinger ◽  
Brian E. Hew ◽  
Bert J.C. Janssen ◽  
Piet Gros ◽  
Carl-Wilhelm Vogel
Keyword(s):  
Amino Acid ◽  
Three Dimensional ◽  
Cobra Venom ◽  
Dimensional Structure ◽  
Amino Acid Residues ◽  
Complement Components ◽  
Cobra Venom Factor ◽  
Three Dimensional Structure ◽  
Factor Function

scholarly journals Efficacy of Dideoxynucleosides against Human Foamy Virus and Relationship to Its Reverse Transcriptase Amino Acid Sequence and Structure

2001 ◽  
Vol 75 (15) ◽  
pp. 7184-7187 ◽  
Author(s):  
Anne Yvon-Groussin ◽  
Pierre Mugnier ◽  
Philippe Bertin ◽  
Marc Grandadam ◽  
Henri Agut ◽  
...  
Keyword(s):  
Amino Acid ◽  
Reverse Transcriptase ◽  
Foamy Virus ◽  
Three Dimensional ◽  
Retroviral Vectors ◽  
Dimensional Structure ◽  
Human Foamy Virus ◽  
Amino Acid Residues ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human foamy virus (HFV), a retrovirus of simian origin which occasionally infects humans, is the basis of retroviral vectors in development for gene therapy. Clinical considerations of how to treat patients developing an uncontrolled infection by either HFV or HFV-based vectors need to be raised. We determined the susceptibility of the HFV to dideoxynucleosides and found that only zidovudine was equally efficient against the replication of human immunodeficiency virus type 1 (HIV-1) and HFV. By contrast, zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), and didanosine (ddI) were 3-, 3-, 30-, and 46-fold less efficient against HFV than against HIV-1, respectively. Some amino acid residues known to be involved in HIV-1 resistance to ddC, 3TC, d4T, and ddI were found at homologous positions of HFV reverse transcriptase (RT). These critical amino acids are located at the same positions in the three-dimensional structure of HIV-1 and HFV RT, suggesting that both enzymes share common patterns of inhibition.

Identification of .beta.-sheet motifs, of .psi.-loops, and of patterns of amino acid residues in three-dimensional protein structures using a subgraph-isomorphism algorithm

1994 ◽  
Vol 34 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Peter J. Artymiuk ◽  
Helen M. Grindley ◽  
Andrew R. Poirrette ◽  
David W. Rice ◽  
Elizabeth C. Ujah ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Structures ◽  
Three Dimensional ◽  
Subgraph Isomorphism ◽  
Beta Sheet ◽  
Amino Acid Residues

Three-dimensional structural aspects of the design of new protein molecules

1986 ◽  
Vol 317 (1540) ◽  
pp. 333-344 ◽  
Keyword(s):  
Tertiary Structure ◽  
Protein Structures ◽  
Three Dimensional ◽  
Spare Parts ◽  
Dimensional Structure ◽  
Sequence Patterns ◽  
Essential Prerequisite ◽  
Structure Of Proteins ◽  
New Protein ◽  
Structural Aspects

A knowledge of the three-dimensional structure of proteins is an essential prerequisite for the design of new molecules. When the tertiary structure is not available from high-resolution X-ray or n.m.r. analysis, the success of prediction is improved by using a relational database of known protein structures. This can be searched to provide information on secondary structure motifs and domains which are recognized by characteristic sequence patterns and which are assembled as ‘spare parts’ by using computer graphics. Similar techniques can be used to give approximate structures for amino-acid replacements, deletions and insertions introduced by mutagenesis. The resulting structures are optimized by using interactive graphics, energy minimization and molecular dynamics.

scholarly journals Protein Structure Prediction Based on Improved Genetic Algorithm

2020 ◽  
Vol 11 (9) ◽  
pp. 450-454
Author(s):  
Jiaxi Liu ◽  
Keyword(s):  
Genetic Algorithm ◽  
Protein Structure ◽  
Amino Acid ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
Protein Structures ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Improved Genetic Algorithm ◽  
Research Areas

The prediction of protein three-dimensional structure from amino acid sequence has been a challenge problem in bioinformatics, owing to the many potential applications for robust protein structure prediction methods. Protein structure prediction is essential to bioscience, and its research results are important for other research areas. Methods for the prediction an才d design of protein structures have advanced dramatically. The prediction of protein structure based on average hydrophobic values is discussed and an improved genetic algorithm is proposed to solve the optimization problem of hydrophobic protein structure prediction. An adjustment operator is designed with the average hydrophobic value to prevent the overlapping of amino acid positions. Finally, some numerical experiments are conducted to verify the feasibility and effectiveness of the proposed algorithm by comparing with the traditional HNN algorithm.

Novel Drug Targets to Overcome De Novo Drug-Resistance In Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3006-3006
Author(s):  
Joel G Turner ◽  
Thomas C Rowe ◽  
David Ostrov ◽  
Jana L Dawson ◽  
Elizabeth Ciaravino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Nuclear Export ◽  
De Novo ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Ic50 Values ◽  
Topo Ii

Abstract Abstract 3006 Abstract Human multiple myeloma (MM) still remains an incurable disease despite improved treatment regimens that include bortezomib, lenalidomide and thalidomide. New therapeutic targets are needed to further improve treatment outcomes. We have shown that targeting intracellular trafficking of proteins may sensitize cells to antitumor agents (Turner et al. 2009, Cancer Res, 69, 6899-905). We have previously demonstrated that topoisomerase II alpha (topo IIα) trafficking from the nucleus to the cytoplasm in myeloma cells occurs by a CRM1-dependent mechanism and resulting in drug resistance to topo II inhibitors (Engel et al. 2004, Exp Cell Res, 295, 421-31). We have also identified the nuclear export signals (NES) for topo IIα at amino acids 1017-28 (site 1) and 1054-66 (site 2) (Turner et al. 2004, J Cell Sci, 117, 3061-71). Blocking nuclear export of topo IIα with a CRM1 inhibitor or by siRNA has been shown to sensitize MM cells to topo II poisons (Turner et al. 2009, Cancer Res, 69, 6899-905). The NES amino acid sequence of topo IIα at 1017–1028 is a unique site. Even though this site conforms to the hydrophobic amino acid motif for an NES, the amino acid sequence does not occur in any other human protein. In addition, this NES is in a pocket formed by the three-dimensional structure of the topo IIα protein. These factors allow the potential for the development of drugs that will exclusively block the NES of topo IIα and not affect the export of other nuclear proteins, as occurs with other known CRM1 inhibitors. Drug resistance to topo II inhibitors occurs when topo IIα is trafficked from the nucleus to the cytoplasm where it is no longer in contact with the DNA, and thus unable to induce cell death (Valkov et al 2000, Br J Haematol, 108, 331-45, Engel et al. 2004, Exp Cell Res, 295, 421-31). We therefore hypothesize that targeting a specific NES in topo IIα is an innovative treatment approach in MM and may allow a very focused and potent combination with topo II inhibitors, possibly overcoming de novo drug resistance in this malignancy. To date, we know of no agents that target the NES of a specific protein that are being developed to treat cancer. A computer generated hybrid molecule using the known three dimensional structure of yeast topo II and the human NES sequences of topo IIα was produced. Molecules were docked in silico using the NCI small molecule database (140,000 compounds). The molecules with the highest docking scores were obtained from NCI and assayed for IC50 values and synergy with the topo II inhibitor doxorubicin. All NES site 1 molecules tested showed activity, however, none of the NES site 2 molecules exhibited any anti-neoplastic activity with or without a topo II inhibitor. CT blue (Promega) robotic cell viability assays determined that several of the site 1 inhibitors had anti-proliferative activity. The IC50 values obtained from single drug cell viability assays in low density cells revealed two site 1 inhibitors compounds with IC50 values of 4.7 (NCI-36400) and 11.1 μM (NCI-35847). None of the site 1 inhibitors affected the viability of high-density cells (IC50>100 μM). Data from apoptosis assays indicate that three of the site 1 inhibitors (NCI-36400, NCI-35847, NCI-35024) that dock to NES site 1 do significantly (p<0.05) sensitize high density MM cells to doxorubicin. Immunofluorescence microscopy revealed an increase in topo IIα in the cell nucleus of cells treated for 20 hours with the three lead site 1 inhibitors. Nuclear-cytoplasmic fractionation revealed that the NES site 1 docking molecules prevent nuclear export of topo IIα. These compounds may lead to new chemotherapeutic treatments of myeloma. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Membrane-Bound Flavocytochromec-Sulfide Dehydrogenase from the Purple Phototrophic Sulfur Bacterium Ectothiorhodospira vacuolata

2000 ◽  
Vol 182 (11) ◽  
pp. 3097-3103 ◽  
Author(s):  
Vesna Kostanjevecki ◽  
Ann Brigé ◽  
Terrance E. Meyer ◽  
Michael A. Cusanovich ◽  
Yves Guisez ◽  
...  
Keyword(s):  
Amino Acid ◽  
Signal Sequence ◽  
Sulfide Oxidation ◽  
Three Dimensional ◽  
Chromatium Vinosum ◽  
Dimensional Structure ◽  
Northern Hybridization ◽  
Amino Acid Residues ◽  
Membrane Bound

ABSTRACT The amino acid sequence of Ectothiorhodospira vacuolatacytochrome c-552, isolated from membranes withn-butanol, shows that it is a protein of 77 amino acid residues with a molecular mass of 9,041 Da. It is closely related to the cytochrome subunit of Chlorobium limicola f. sp.thiosulfatophilum flavocytochrome c-sulfide dehydrogenase (FCSD), having 49% identity. These data allowed isolation of a 5.5-kb subgenomic clone which contains the cytochrome gene and an adjacent flavoprotein gene as in other species which have an FCSD. The cytochrome subunit has a signal peptide with a normal cleavage site, but the flavoprotein subunit has a signal sequence which suggests that the mature protein has an N-terminal cysteine, characteristic of a diacyl glycerol-modified lipoprotein. The membrane localization of FCSD was confirmed by Western blotting with antibodies raised against Chromatium vinosum FCSD. When aligned according to the three-dimensional structure of ChromatiumFCSD, all but one of the side chains near the flavin are conserved. These include the Cys 42 flavin adenine dinucleotide binding site; the Cys 161-Cys 337 disulfide; Glu 167, which modulates the reactivity with sulfite; and aromatic residues which may function as charge transfer acceptors from the flavin-sulfite adduct (C. vinosumnumbering). The genetic context of FCSD is different from that in other species in that flanking genes are not conserved. The transcript is only large enough to encode the two FCSD subunits. Furthermore, Northern hybridization showed that the production of E. vacuolata FCSD mRNA is regulated by sulfide. All cultures that contained sulfide in the medium had elevated levels of FCSD RNA compared with cells grown on organics (acetate, malate, or succinate) or thiosulfate alone, consistent with the role of FCSD in sulfide oxidation.

scholarly journals PROCARB: A Database of Known and Modelled Carbohydrate-Binding Protein Structures with Sequence-Based Prediction Tools

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Adeel Malik ◽  
Ahmad Firoz ◽  
Vivekanand Jha ◽  
Shandar Ahmad
Keyword(s):  
Binding Sites ◽  
De Novo ◽  
Solvent Accessibility ◽  
Protein Structures ◽  
Three Dimensional ◽  
Data Bank ◽  
Dimensional Structure ◽  
Carbohydrate Binding ◽  
Structural And Functional Properties ◽  
Three Dimensional Models

Understanding of the three-dimensional structures of proteins that interact with carbohydrates covalently (glycoproteins) as well as noncovalently (protein-carbohydrate complexes) is essential to many biological processes and plays a significant role in normal and disease-associated functions. It is important to have a central repository of knowledge available about these protein-carbohydrate complexes as well as preprocessed data of predicted structures. This can be significantly enhanced by tools de novo which can predict carbohydrate-binding sites for proteins in the absence of structure of experimentally known binding site. PROCARB is an open-access database comprising three independently working components, namely, (i) Core PROCARB module, consisting of three-dimensional structures of protein-carbohydrate complexes taken from Protein Data Bank (PDB), (ii) Homology Models module, consisting of manually developed three-dimensional models of N-linked and O-linked glycoproteins of unknown three-dimensional structure, and (iii) CBS-Pred prediction module, consisting of web servers to predict carbohydrate-binding sites using single sequence or server-generated PSSM. Several precomputed structural and functional properties of complexes are also included in the database for quick analysis. In particular, information about function, secondary structure, solvent accessibility, hydrogen bonds and literature reference, and so forth, is included. In addition, each protein in the database is mapped to Uniprot, Pfam, PDB, and so forth.

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