Foldamers containing γ-amino acid residues or their analogues: structural features and applications

Amino Acids ◽  
2011 ◽  
Vol 41 (3) ◽  
pp. 687-707 ◽  
Author(s):  
Francelin Bouillère ◽  
Sophie Thétiot-Laurent ◽  
Cyrille Kouklovsky ◽  
Valérie Alezra
Keyword(s):  
Amino Acid ◽  
Structural Features ◽  
Amino Acid Residues

scholarly journals Multiple Distinct Sets of Stereotyped Antigen Receptors Indicate a Role for Antigen in Promoting Chronic Lymphocytic Leukemia

2004 ◽  
Vol 200 (4) ◽  
pp. 519-525 ◽  
Author(s):  
Bradley T. Messmer ◽  
Emilia Albesiano ◽  
Dimitar G. Efremov ◽  
Fabio Ghiotto ◽  
Steven L. Allen ◽  
...  
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Structural Features ◽  
Lymphocytic Leukemia ◽  
Cell Subpopulation ◽  
Amino Acid Residues ◽  
Antigen Receptors ◽  
Region Gene ◽  
V Region ◽  
Unique Amino Acid

Previous studies suggest that the diversity of the expressed variable (V) region repertoire of the immunoglobulin (Ig)H chain of B-CLL cells is restricted. Although limited examples of marked constraint in the primary structure of the H and L chain V regions exist, the possibility that this level of restriction is a general principle in this disease has not been accepted. This report describes five sets of patients, mostly with unmutated or minimally mutated IgV genes, with strikingly similar B cell antigen receptors (BCRs) arising from the use of common H and L chain V region gene segments that share CDR3 structural features such as length, amino acid composition, and unique amino acid residues at recombination junctions. Thus, a much more striking degree of structural restriction of the entire BCR and a much higher frequency of receptor sharing exists among patients than appreciated previously. The data imply that either a significant fraction of B-CLL cells was selected by a limited set of antigenic epitopes at some point in their development and/or that they derive from a distinct B cell subpopulation with limited Ig V region diversity. These shared, stereotyped Ig molecules may be valuable probes for antigen identification and important targets for cross-reactive idiotypic therapy.

scholarly journals The influence of sex steroid hormones on ferrochelatase gene expression in Harderian gland of hamster (Mesocricetus auratus)

2006 ◽  
Vol 189 (1) ◽  
pp. 103-112 ◽  
Author(s):  
F Vilchis ◽  
L Ramos ◽  
C Timossi ◽  
B Chávez
Keyword(s):  
Amino Acid ◽  
Steroid Hormones ◽  
Protoporphyrin Ix ◽  
Harderian Gland ◽  
Active Role ◽  
Structural Features ◽  
Sex Steroid Hormones ◽  
Sex Steroid ◽  
Amino Acid Residues ◽  
Haem Proteins

Ferrochelatase (protohaem ferrolyase, EC 4.99.1.1), the terminal enzyme of the haem biosynthetic pathway, catalyses the insertion of ferrous iron into protoporphyrin IX to form protohaem. The Syrian hamster Harderian gland (HG) is known for its ability to produce and accumulate large amounts of protoporphyrins. In this species, the female gland contains up to 120 times more porphyrin than the male gland. Data from biochemical studies suggest that this gland possesses the enzymatic complex for haem biosynthesis but lacks ferrochelatase activity. The abundance of intraglandular haem proteins does not support this idea. To gain more insight into this process, we isolated cDNA for ferrochelatase from hamster liver, using the 5′- and 3′- rapid amplification of complementary DNA ends (RACE), and investigated its expression in HG from males and females. The full-length cDNA comprises an open reading frame of 1269 bp encoding a polypeptide of 422 amino-acid residues. Hamster DNA sequence exhibits 92% identity to mouse and 87% identity to human sequences. The predicted hamster enzyme was shown to have structural features of mammalian ferrochelatase, including a putative NH2- terminal presequence, a central core of about 330 amino-acid residues and an extra 30–50-amino-acid stretch at the carboxyl-terminus. RNA blotting experiments indicated that this cDNA hybridized to a liver mRNA of about 2.1 kb, while a weak hybridization signal was observed with mRNA from HG preparations. RT–PCR assays confirmed the expression of specific transcripts in both tissues. Male glands contained approximately twofold more enzyme mRNA than female glands. Likewise, the intraglandular content of mRNA varied during the oestrous cycle, with the highest levels found in the oestrous phase. These cyclic variations were less evident in liver. Ovariectomy plus treatment with progesterone or 17β-oestradiol plus progesterone increased ferrochelatase mRNA of the gland. In HG of short- or long-term castrated males, the administration of testosterone did not affect the ferrochelatase mRNA concentration. Based on mRNA expression levels, we conclude that Harderian ferrochelatase may play an active role in maintaining the physiological pool of haem required for processing cytochromes and other glandular haem proteins. Likewise, the sex-steroid hormones appear to have only a modest influence upon Harderian ferrochelatase.

scholarly journals Three Structural Features of Functional Food Components and Herbal Medicine with Amyloid β42 Anti-Aggregation Properties

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2125 ◽  
Author(s):  
Kazuma Murakami ◽  
Kazuhiro Irie
Keyword(s):  
Amino Acid ◽  
Functional Food ◽  
Structural Characteristics ◽  
Salt Bridge ◽  
Basic Amino Acid ◽  
Structural Features ◽  
Amino Acid Residues ◽  
Treatment And Prevention ◽  
Food Components ◽  
Underlying Mechanisms

Aggregation of amyloid β42 (Aβ42) is one of the hallmarks of Alzheimer’s disease (AD). There are numerous naturally occurring products that suppress the aggregation of Aβ42, but the underlying mechanisms remain to be elucidated. Based on NMR and MS spectroscopic analysis, we propose three structural characteristics found in natural products required for the suppressive activity against Aβ42 aggregation (i.e., oligomerization by targeting specific amino acid residues on this protein). These characteristics include (1) catechol-type flavonoids that can form Michael adducts with the side chains of Lys16 and 28 in monomeric Aβ42 through flavonoid autoxidation; (2) non-catechol-type flavonoids with planarity due to α,β-unsaturated carbonyl groups that can interact with the intermolecular β-sheet region in Aβ42 aggregates, especially aromatic rings such as those of Phe19 and 20; and (3) carboxy acid derivatives with triterpenoid or anthraquinoid that can generate a salt bridge with basic amino acid residues such as Lys16 and 28 in the Aβ42 dimer or trimer. Here, we summarize the recent body of knowledge concerning amyloidogenic inhibitors, particularly in functional food components and Kampo medicine, and discuss their application in the treatment and prevention of AD.

scholarly journals H-2Kd-restricted antigenic peptides share a simple binding motif.

1991 ◽  
Vol 174 (3) ◽  
pp. 603-612 ◽  
Author(s):  
P Romero ◽  
G Corradin ◽  
I F Luescher ◽  
J L Maryanski
Keyword(s):  
Amino Acid ◽  
Mhc Class I ◽  
Specific Binding ◽  
Structural Features ◽  
Class I ◽  
Binding Motif ◽  
Antigenic Peptides ◽  
Amino Acid Residues ◽  
Antigenic Activity ◽  
Mhc Class I Molecule

We have defined structural features that are apparently important for the binding of four different, unrelated antigenic epitopes to the same major histocompatibility complex (MHC) class I molecule, H-2Kd. The four epitopes are recognized in the form of synthetic peptides by cytotoxic T lymphocytes of the appropriate specificity. By analysis of the relative potency of truncated peptides, we demonstrated that for each of the four epitopes, optimal antigenic activity was present in a peptide of 9 or 10 amino acid residues. A comparison of the relative competitor activity of the different-length peptides in a functional competition assay, as well as in a direct binding assay based on photoaffinity labeling of the Kd molecule, indicated that the enhanced potency of the peptides upon reduction in length was most likely due to a higher affinity of the shorter peptides for the Kd molecule. A remarkably simple motif that appears to be important for the specific binding of Kd-restricted peptides was identified by the analysis of peptides containing amino acid substitutions or deletions. The motif consists of two elements, a Tyr in the second position relative to the NH2 terminus and a hydrophobic residue with a large aliphatic side chain (Leu, Ile, or Val) at the COOH-terminal end of the optimal 9- or 10-mer peptides. We demonstrated that a simple peptide analogue (AYP6L) that incorporates the motif can effectively and specifically interact with the Kd molecule. Moreover, all of the additional Kd-restricted epitopes defined thus far in the literature contain the motif, and it may thus be useful for the prediction of new epitopes recognized by T cells in the context of this MHC class I molecule.

scholarly journals Structural analyses of the deduced amino acid sequences of a novel type heme–copper terminal oxidase, cytochrome aco3, from alkalophilic Bacillus YN-2000

2001 ◽  
Vol 47 (12) ◽  
pp. 1075-1081 ◽  
Author(s):  
Kimitoshi Denda ◽  
Akira Oshima ◽  
Yoshihiro Fukumori
Keyword(s):  
Amino Acid ◽  
Cytochrome C ◽  
Basic Amino Acid ◽  
Structural Features ◽  
Thermophilic Bacterium ◽  
Amino Acid Sequences ◽  
Amino Acid Residues ◽  
Gene Encoding ◽  
Bacterium Bacillus ◽  
Alkalophilic Bacillus

Cytochrome aco3 from a facultatively alkalophilic bacterium, Bacillus YN-2000, was found to be alkaline- and heat-tolerant. To better understand the structural features of Bacillus YN-2000 cytochrome aco3, the gene encoding this enzyme was cloned and sequenced. Nucleotide sequence analyses of the region neighboring the acoI (subunit I) gene revealed that the acoII (subunit II) and acoIII (subunit III) genes were concomitantly clustered upstream and downstream of the acoI gene, respectively, forming an operon with transcriptional polarity. The deduced amino acid sequence of subunit I was highly similar to that of cytochrome caa3 from thermophilic bacterium Bacillus PS3 in which the heme a3 could be replaced with heme o. Furthermore, a marked paucity of basic amino acid residues was found in the cytochrome c-binding subunit II, which might be a result of the adaptation to a highly alkaline external milieu.Key words: cytochrome c oxidase, alkalophile, thermostability, heme o, Bacilli.

scholarly journals The aminoacylation of transfer ribonucleic acid. Inhibitory effects of some amino acid analogues with altered side chains

1976 ◽  
Vol 159 (3) ◽  
pp. 503-511 ◽  
Author(s):  
J M Old ◽  
D S Jones
Keyword(s):  
Amino Acid ◽  
Rat Liver ◽  
Structural Features ◽  
Biologically Active ◽  
Side Chains ◽  
Amino Acid Residues ◽  
Trna Synthetases ◽  
E Coli ◽  
Amino Acid Side Chains ◽  
Amino Acid Analogues

Several amino acid analogues that are able to replace amino acid residues in binding positions of the biologically active C-terminal tetrapeptide amide sequence, Trp-Met-Asp-PheNH2, of the gastrins were examined for their ability to inhibit the aminoacylation of tRNA in an Escherichia coli and rat liver system. Although in both systems the amino acid side chains are involved in the recognition process, the structural requirements of the side chain in the two systems are not comparable. Analogues of methionine and phenylalanine behaved similarly in the E. coli and rat liver systems, whereas analogues of tryptophan behaved differently. From the results it is possible to suggest structural features of the amino acid side chains which are required for recognition by the aminoacyl-tRNA synthetases.

scholarly journals THE STRUCTURAL BASIS FOR BINDING OF COMPLEMENT BY IMMUNOGLOBULIN M

1974 ◽  
Vol 140 (4) ◽  
pp. 1117-1121 ◽  
Author(s):  
Mary M. Hurst ◽  
John E. Volanakis ◽  
Raymond B. Hester ◽  
Robert M. Stroud ◽  
J. Claude Bennett
Keyword(s):  
Amino Acid ◽  
Structural Features ◽  
Immunoglobulin M ◽  
Structural Basis ◽  
Amino Acid Residues ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Carboxy Terminal ◽  
Insight Into

An insight into the structural features of human IgM that are responsible for its capacity to bind the first component of complement (C) has been obtained by examining the ability of IgM subfragments to bind active C1 (C1). The smallest two fragments found to bind C1 were the major CNBr fragment of the Fc portion of IgM and the CH4 fragment of the carboxy-terminal domain. The smallest fragment which fixes C1 has a disaggregated mol wt of 6,800, consists of 60 residues, and contains no carbohydrate. Structural considerations and sequence overlaps suggest that the amino-terminal side of the CH4 domain (24 amino acid residues) might be responsible for fixing C1.

scholarly journals Primary structure of a dimeric haemoglobin from the deep-sea cold-seep clam Calyptogena soyoae

1989 ◽  
Vol 260 (1) ◽  
pp. 177-182 ◽  
Author(s):  
T Suzuki ◽  
T Takagi ◽  
S Ohta
Keyword(s):  
Amino Acid ◽  
Structural Features ◽  
Amino Acid Sequences ◽  
Cold Seep ◽  
Intact Protein ◽  
British Library ◽  
Amino Acid Residues ◽  
Sagami Bay ◽  
Human Haemoglobin ◽  
Subunit Assembly

The heterodont clam Calyptogena soyoae, living in the cold-seep area of the upper bathyal depth of Sagami Bay, Japan, has two homodimeric haemoglobins (Hb I and Hb II) in erythrocytes. The complete amino acid sequence of 136 residues of C. soyoae Hb II was determined. The sequence showed low homology with any other globins (at most 20% identity) and lacked the N-terminal extension of seven to nine amino acid residues characteristic of all the molluscan haemoglobins sequenced hitherto. Although the subunit assembly of molluscan haemoglobin is known to be ‘back-to-front’ relative to vertebrate haemoglobin, C. soyoae Hb II is unlikely to undergo such a subunit assembly because it lacks homology in the sequence involving subunit interaction. These structural features suggest that C. soyoae haemoglobin may have accomplished a unique molecular evolution. The distal (E7) histidine residue of C. soyoae Hb II is unusually replaced by glutamine. However, the oxyhaemoglobin is stable enough to act as an O2 carrier, since the autoxidation rate at near physiological temperature (3 degrees C) is about 3 times lower than that of human haemoglobin at 37 degrees C. H.p.l.c. patterns of peptides (Figs. 5-7), amino acid compositions of intact protein and peptides (Table 1) and amino acid sequences of intact protein and peptides (Tables 2 and 3) have been deposited as Supplementary Publication SUP 50150 (11 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms indicated in Biochem. J. (1989) 257, 5.

Identification of key residues in the formate channel FocA that control import and export of formate

2014 ◽  
Vol 395 (7-8) ◽  
pp. 813-825 ◽  
Author(s):  
Doreen Hunger ◽  
Claudia Doberenz ◽  
R. Gary Sawers
Keyword(s):  
Amino Acid ◽  
Quaternary Structure ◽  
Salt Bridge ◽  
Structural Features ◽  
Amino Acid Residues ◽  
Form Part ◽  
Import And Export ◽  
Key Residues ◽  
Acid Exchange

Abstract The formate-nitrite transporter (FNT) family comprises pentameric channels that transport monovalent anions. The prototype of this family is the formate channel (FocA), which was originally identified as a formate channel in Escherichia coli. Each protomer in the channel has a pore with structural features that include periplasmic and cytoplasmic constriction sites, which are likely important for bi-directional gating of substrate passage. Highly conserved amino acid residues within FocA previously identified in structural studies are predicted to be important in the control of formate translocation. Here we present a first detailed in vivo analysis of these residues using a combined targeted amino acid exchange and formate-responsive lacZ fusion-based reporter approach. Sixteen exchanges were made and each variant was shown to be largely unaffected in its secondary and quaternary structure. The invariant H209 and T91 residues, which form part of the lower constriction site linking the Ω-loop with the pore cavity, proved to be important in governing the directionality of formate passage through the pore. A predicted salt-bridge triad of E208-K156-N213 along with the cytoplasmically-oriented N-terminal helix are also involved in pH-dependent gating of the channel. Together, our data are consistent with passive export and import of formate or formic acid through the channel.

Structures and target recognition modes of PDZ domains: recurring themes and emerging pictures

2013 ◽  
Vol 455 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Fei Ye ◽  
Mingjie Zhang
Keyword(s):  
Amino Acid ◽  
Pdz Domain ◽  
Binding Mode ◽  
Structural Features ◽  
Scaffold Proteins ◽  
Amino Acid Residues ◽  
Pdz Domains ◽  
Target Proteins ◽  
Protein Protein Interaction ◽  
Target Binding

PDZ domains are highly abundant protein–protein interaction modules and are often found in multidomain scaffold proteins. PDZ-domain-containing scaffold proteins regulate multiple biological processes, including trafficking and clustering receptors and ion channels at defined membrane regions, organizing and targeting signalling complexes at specific cellular compartments, interfacing cytoskeletal structures with membranes, and maintaining various cellular structures. PDZ domains, each with ~90-amino-acid residues folding into a highly similar structure, are best known to bind to short C-terminal tail peptides of their target proteins. A series of recent studies have revealed that, in addition to the canonical target-binding mode, many PDZ–target interactions involve amino acid residues beyond the regular PDZ domain fold, which we refer to as extensions. Such extension sequences often form an integral structural and functional unit with the attached PDZ domain, which is defined as a PDZ supramodule. Correspondingly, PDZ-domain-binding sequences from target proteins are frequently found to require extension sequences beyond canonical short C-terminal tail peptides. Formation of PDZ supramodules not only affords necessary binding specificities and affinities demanded by physiological functions of PDZ domain targets, but also provides regulatory switches to be built in the PDZ–target interactions. At the 20th anniversary of the discovery of PDZ domain proteins, we try to summarize structural features and target-binding properties of such PDZ supramodules emerging from studies in recent years.

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