Pb2+ binding to lentil lectin and its influence on the protein aggregation

RSC Advances ◽  
2015 ◽  
Vol 5 (88) ◽  
pp. 72352-72360
Author(s):  
Atul Gajanan Thawari ◽  
Khatija Tabbasum ◽  
Vijaya Kumar Hinge ◽  
Chebrolu Pulla Rao
Keyword(s):  
Protein Aggregation ◽  
Structural Changes ◽  
Side Chain ◽  
Lentil Lectin

The Pb2+ binds through the side chain carboxylate and imidazole moieties of the lentil lectin by bringing some secondary structural changes. As a result of this the original aggregates of the simple protein disaggregates upon binding to Pb2+.

scholarly journals Structure-Activity Relationships of Sandalwood Odorants: Synthesis of a New Campholene Derivative

2010 ◽  
Vol 5 (9) ◽  
pp. 1934578X1000500
Author(s):  
Iris Stappen ◽  
Joris Höfinghoff ◽  
Gerhard Buchbauer ◽  
Peter Wolschann
Keyword(s):  
Structural Changes ◽  
Great Influence ◽  
Complete Loss ◽  
Side Chain ◽  
Side Chains ◽  
Quaternary Carbon ◽  
Structural Modifications ◽  
Structure Activity ◽  
Highly Sensitive ◽  
Sandalwood Odorants

Structural modifications of natural (-)-( Z)-β-santalol have shown that the sandalwood odor impression is highly sensitive, even to small structural changes. Particularly, the substitution of the quaternary carbon is of great influence on the scent. Epi-compounds with side chains in the endo-position possess sandalwood odor in only a few derivatives, whereas modifications at this side chain, as well as modification at the bicyclic ring systems mostly lead to a complete loss of sandalwood fragrance.

scholarly journals Catalysis of Hydrazone and Oxime Peptide Ligation by Arginine

2020 ◽  
Author(s):  
Nathalie Ollivier ◽  
Vangelis Agouridas ◽  
Benoît Snella ◽  
Rémi Desmet ◽  
Hervé Drobecq ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Phosphate Buffer ◽  
Side Chain ◽  
Neutral Ph ◽  
Arginine Hydrochloride ◽  
Guanidinium Group ◽  
Aggregation Inhibitor ◽  
Peptide Ligation

Hydrazone and oxime peptide ligations are catalyzed by arginine. The catalysis is assisted intramolecularly by the side-chain guanidinium group. Hydrazone ligation in the presence of arginine proceeds efficiently in phosphate buffer at neutral pH but is particularly powerful in bicarbonate/CO<sub>2</sub> buffer. In addition to acting as a catalyst, arginine prevents the aggregation of proteins during ligation. With its dual properties as nucleophilic catalyst and protein aggregation inhibitor, arginine hydrochloride is a useful addition to the hydrazone/oxime ligation toolbox.<br>

Effects of heme modification on oxygen affinity and cooperativity of human adult hemoglobin

2015 ◽  
Vol 19 (01-03) ◽  
pp. 301-307 ◽  
Author(s):  
Tomokazu Shibata ◽  
Eisuke Furuichi ◽  
Kiyohiro Imai ◽  
Akihiro Suzuki ◽  
Yasuhiko Yamamoto
Keyword(s):  
Structural Changes ◽  
Oxygen Affinity ◽  
Side Chain ◽  
Side Chains ◽  
Human Adult ◽  
Alkaline Transition ◽  
Functional Control ◽  
Adult Hemoglobin ◽  
The Relationship ◽  
Heme Cofactor

We substituted strongly electron-withdrawing trifluoromethyl ( CF 3) group(s) as heme side chain(s) of human adult hemoglobin (Hb) to achieve large alterations of the heme electronic structure, in order to elucidate the relationship between the oxygen ( O 2) binding properties of Hb and the electronic properties of heme peripheral side chains. The obtained results were compared with those of similar studies performed on myoglobin (Mb), e.g. (Nishimura R, Matsumoto D, Shibata T, Yanagisawa S, Ogura T, Tai H, Matsuo T, Hirota S, Neya S, Suzuki A, and Yamamoto Y. Inorg. Chem. 2014; 53: 9156–9165). These two proteins shared the common feature of a decrease in O 2 affinity upon the CF 3 substitution(s). Using the P50 value, which is the partial pressure of O 2 required for 50% oxygenation of a protein, and the equilibrium constant ( p K a ) of the "acid-alkaline transition" in the met form of a protein as measures of the O 2 affinity and the electron density of heme Fe atom of the protein, respectively, a linear p K a - log (1/P50) relationship was demonstrated for the Hb and Mb systems. The native Hb, however, deviated from the p K a - log (1/P50) relationship, while the native Mb followed it. These results highlighted the significance of the vinyl side chains of the heme cofactor in the functional control of Hb through tertiary and quaternary structural changes upon the oxygenation of the protein.

Raman Spectroscopic Evidence for Side-Chain Unfolding in Spider Dragline Silk under Tensile Deformation

2005 ◽  
Vol 874 ◽  
Author(s):  
Xiaojun He ◽  
Michael S. Ellison ◽  
Jacqueline M. Palmer
Keyword(s):  
Structural Changes ◽  
Tensile Deformation ◽  
Raman Band ◽  
Side Chain ◽  
Dragline Silk ◽  
Spider Dragline Silk ◽  
Raman Spectroscopic ◽  
Lateral Coupling ◽  
Silk Peptide ◽  
Random Configuration

AbstractIn-situ Ramanspectra were collected on the N. clavipes spider dragline silk under a tensile deformation rate of 15mm/min. The most prominent features on the spectra were due to those bands near 1100 cm-1, which present as a sensitive probe to structural changes associated with side-chains of silk peptide. A downshift of Raman bands at 1095 cm-1 and 1089 cm-1 was detected with increasing strain. Furthermore, an increase in the intensity of the Raman band at 1062 cm-1 due to the vibration of trans structure without lateral coupling was prominent at certain strain levels. This was interpreted in terms of a morphology transition from the random configuration to the trans conformation modulated by the reorganization of the hydrogen bonding among the side-chain.

scholarly journals Deciphering the Evolution of Cephalosporin Resistance to Ceftolozane-Tazobactam in Pseudomonas aeruginosa

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Melissa D. Barnes ◽  
Magdalena A. Taracila ◽  
Joseph D. Rutter ◽  
Christopher R. Bethel ◽  
Ioannis Galdadas ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Conformational Changes ◽  
Structural Changes ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Single Amino Acid ◽  
Side Chain ◽  
Diffusion Limit ◽  
Content Type ◽  
Lactamase Inhibitor

ABSTRACT Pseudomonas aeruginosa produces a class C β-lactamase (e.g., PDC-3) that robustly hydrolyzes early generation cephalosporins often at the diffusion limit; therefore, bacteria possessing these β-lactamases are resistant to many β-lactam antibiotics. In response to this significant clinical threat, ceftolozane, a 3′ aminopyrazolium cephalosporin, was developed. Combined with tazobactam, ceftolozane promised to be effective against multidrug-resistant P. aeruginosa. Alarmingly, Ω-loop variants of the PDC β-lactamase (V213A, G216R, E221K, E221G, and Y223H) were identified in ceftolozane/tazobactam-resistant P. aeruginosa clinical isolates. Herein, we demonstrate that the Escherichia coli strain expressing the E221K variant of PDC-3 had the highest minimum inhibitory concentrations (MICs) against a panel of β-lactam antibiotics, including ceftolozane and ceftazidime, a cephalosporin that differs in structure largely in the R2 side chain. The kcat values of the E221K variant for both substrates were equivalent, whereas the Km for ceftolozane (341 ± 64 µM) was higher than that for ceftazidime (174 ± 20 µM). Timed mass spectrometry, thermal stability, and equilibrium unfolding studies revealed key mechanistic insights. Enhanced sampling molecular dynamics simulations identified conformational changes in the E221K variant Ω-loop, where a hidden pocket adjacent to the catalytic site opens and stabilizes ceftolozane for efficient hydrolysis. Encouragingly, the diazabicyclooctane β-lactamase inhibitor avibactam restored susceptibility to ceftolozane and ceftazidime in cells producing the E221K variant. In addition, a boronic acid transition state inhibitor, LP-06, lowered the ceftolozane and ceftazidime MICs by 8-fold for the E221K-expressing strain. Understanding these structural changes in evolutionarily selected variants is critical toward designing effective β-lactam/β-lactamase inhibitor therapies for P. aeruginosa infections. IMPORTANCE The presence of β-lactamases (e.g., PDC-3) that have naturally evolved and acquired the ability to break down β-lactam antibiotics (e.g., ceftazidime and ceftolozane) leads to highly resistant and potentially lethal Pseudomonas aeruginosa infections. We show that wild-type PDC-3 β-lactamase forms an acyl enzyme complex with ceftazidime, but it cannot accommodate the structurally similar ceftolozane that has a longer R2 side chain with increased basicity. A single amino acid substitution from a glutamate to a lysine at position 221 in PDC-3 (E221K) causes the tyrosine residue at 223 to adopt a new position poised for efficient hydrolysis of both cephalosporins. The importance of the mechanism of action of the E221K variant, in particular, is underscored by its evolutionary recurrences in multiple bacterial species. Understanding the biochemical and molecular basis for resistance is key to designing effective therapies and developing new β-lactam/β-lactamase inhibitor combinations.

scholarly journals Structural and biochemical basis of the formation of isoaspartate in the complementarity-determining region of antibody 64M-5 Fab

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hideshi Yokoyama ◽  
Ryuta Mizutani ◽  
Shuji Noguchi ◽  
Naoki Hayashida
Keyword(s):  
Normal Form ◽  
Electrostatic Interactions ◽  
Structural Changes ◽  
Peptide Mapping ◽  
Exchange Chromatography ◽  
Side Chain ◽  
Type I ◽  
Biochemical Basis ◽  
Structural Conversion ◽  
Complementarity Determining Region

AbstractThe formation of the isoaspartate (isoAsp) is one of spontaneous degradation processes of proteins, affecting their stability and activity. Here, we report for the first time the crystal structures of an antibody Fab that contains isoAsp in the complementarity-determining region (CDR), along with biochemical studies to detect isoAsp. By comparing the elution profiles of cation-exchange chromatography, it was clarified that the antibody 64M-5 Fab is converted from the normal form to isoAsp form spontaneously and time-dependently under physiological conditions. The isoAsp residue was identified with tryptic peptide mapping, N-terminal sequencing, and the protein isoaspartyl methyltransferase assay. Based on the fluorescence quenching method, the isoAsp form of 64M-5 Fab shows a one order of magnitude lower binding constant for its dinucleotide ligand dT(6–4)T than the normal form. According to the structure of the isoAsp form, the conformation of CDR L1 is changed from the normal form to isoAsp form; the loss of hydrogen bonds involving the Asn28L side-chain, and structural conversion of the β-turn from type I to type II’. The formation of isoAsp leads to a large displacement of the side chain of His27dL, and decreased electrostatic interactions with the phosphate group of dT(6–4)T. Such structural changes should be responsible for the lower affinity of the isoAsp form for dT(6–4)T than the normal form. These findings may provide insight into neurodegenerative diseases (NDDs) and related diseases caused by misfolded proteins.

scholarly journals Suppression of conformational heterogeneity at a protein–protein interface

2015 ◽  
Vol 112 (29) ◽  
pp. 9028-9033 ◽  
Author(s):  
Lindsay N. Deis ◽  
Qinglin Wu ◽  
You Wang ◽  
Yang Qi ◽  
Kyle G. Daniels ◽  
...  
Keyword(s):  
Structural Changes ◽  
Tertiary Structure ◽  
Protein A ◽  
Side Chain ◽  
Host Immune System ◽  
Conformational Heterogeneity ◽  
Staphylococcal Protein A ◽  
Protein Interface ◽  
Multiple Binding ◽  
Important Virulence Factor

Staphylococcal protein A (SpA) is an important virulence factor from Staphylococcus aureus responsible for the bacterium’s evasion of the host immune system. SpA includes five small three-helix–bundle domains that can each bind with high affinity to many host proteins such as antibodies. The interaction between a SpA domain and the Fc fragment of IgG was partially elucidated previously in the crystal structure 1FC2. Although informative, the previous structure was not properly folded and left many substantial questions unanswered, such as a detailed description of the tertiary structure of SpA domains in complex with Fc and the structural changes that take place upon binding. Here we report the 2.3-Å structure of a fully folded SpA domain in complex with Fc. Our structure indicates that there are extensive structural rearrangements necessary for binding Fc, including a general reduction in SpA conformational heterogeneity, freezing out of polyrotameric interfacial residues, and displacement of a SpA side chain by an Fc side chain in a molecular-recognition pocket. Such a loss of conformational heterogeneity upon formation of the protein–protein interface may occur when SpA binds its multiple binding partners. Suppression of conformational heterogeneity may be an important structural paradigm in functionally plastic proteins.

scholarly journals Catalysis of Hydrazone and Oxime Peptide Ligation by Arginine

2020 ◽  
Author(s):  
Nathalie Ollivier ◽  
Vangelis Agouridas ◽  
Benoît Snella ◽  
Rémi Desmet ◽  
Hervé Drobecq ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Phosphate Buffer ◽  
Side Chain ◽  
Neutral Ph ◽  
Arginine Hydrochloride ◽  
Guanidinium Group ◽  
Aggregation Inhibitor ◽  
Peptide Ligation

Hydrazone and oxime peptide ligations are catalyzed by arginine. The catalysis is assisted intramolecularly by the side-chain guanidinium group. Hydrazone ligation in the presence of arginine proceeds efficiently in phosphate buffer at neutral pH but is particularly powerful in bicarbonate/CO<sub>2</sub> buffer. In addition to acting as a catalyst, arginine prevents the aggregation of proteins during ligation. With its dual properties as nucleophilic catalyst and protein aggregation inhibitor, arginine hydrochloride is a useful addition to the hydrazone/oxime ligation toolbox.<br>

scholarly journals Advanced glycation end products (AGEs), protein aggregation and their cross talk: new insight in tumorigenesis

Glycobiology ◽  
2019 ◽  
Vol 30 (1) ◽  
pp. 2-18
Author(s):  
Ejazul Haque ◽  
Mohd Kamil ◽  
Adria Hasan ◽  
Safia Irfan ◽  
Saba Sheikh ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Advanced Glycation End Products ◽  
Cross Talk ◽  
Structural Changes ◽  
Current Knowledge ◽  
Normal Function ◽  
Protein Glycation ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Abstract Protein glycation and protein aggregation are two distinct phenomena being observed in cancer cells as factors promoting cancer cell viability. Protein aggregation is an abnormal interaction between proteins caused as a result of structural changes in them after any mutation or environmental assault. Protein aggregation is usually associated with neurodegenerative diseases like Alzheimer’s and Parkinson’s, but of late, research findings have shown its association with the development of different cancers like lung, breast and ovarian cancer. On the contrary, protein glycation is a cascade of irreversible nonenzymatic reaction of reducing sugar with the amino group of the protein resulting in the modification of protein structure and formation of advanced glycation end products (AGEs). These AGEs are reported to obstruct the normal function of proteins. Lately, it has been reported that protein aggregation occurs as a result of AGEs. This aggregation of protein promotes the transformation of healthy cells to neoplasia leading to tumorigenesis. In this review, we underline the current knowledge of protein aggregation and glycation along with the cross talk between the two, which may eventually lead to the development of cancer.

1α,25-dihydroxyvitamin D3 hybrid analogs with structural changes at both the A-ring and the C,D-ring side-chain

1994 ◽  
Vol 4 (24) ◽  
pp. 2919-2924 ◽  
Author(s):  
Gary H. Posner ◽  
M.Christina White ◽  
Patrick Dolan ◽  
Thomas W. Kensler ◽  
Shigefumi Yukihiro ◽  
...  
Keyword(s):  
Structural Changes ◽  
Side Chain ◽  
Dihydroxyvitamin D3
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