Mechanistic Basis for Site–Site Interactions in Inhibitor and Substrate Binding to Band 3 (AE1): Evidence Distinguishing Allosteric from Electrostatic Effects

2001 ◽  
Vol 27 (5) ◽  
pp. 901-912 ◽  
Author(s):  
James M. Salhany
Keyword(s):  
Substrate Binding ◽  
Band 3 ◽  
Electrostatic Effects ◽  
Mechanistic Basis

Influence of Stilbene Disulfonates on the Accessibility of the Substrate-Binding Site for Anions in the Band 3 Protein (AEB1)

1994 ◽  
Vol 17 (3-4) ◽  
pp. 187-189
Author(s):  
N. Araníbar ◽  
C. Ostermeier ◽  
B. Legrum ◽  
H. Rüterjans ◽  
H. Passow
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Band 3 ◽  
Band 3 Protein ◽  
Substrate Binding Site

scholarly journals The Advantages of Being Locked

2007 ◽  
Vol 282 (49) ◽  
pp. 35510-35518 ◽  
Author(s):  
Stefano Donini ◽  
Marcello Clerici ◽  
Jesper Wengel ◽  
Birte Vester ◽  
Alessio Peracchi
Keyword(s):  
Human Papillomavirus ◽  
Rna Structure ◽  
Substrate Binding ◽  
Locked Nucleic Acid ◽  
Association Rate ◽  
Kinetics And Thermodynamics ◽  
Substrate Complex ◽  
Human Papillomavirus Type 16 ◽  
Mrna Structure ◽  
Mechanistic Basis

RNA-cleaving deoxyribozymes can be used for the sequence-specific knockdown of mRNAs. It was previously shown that activity of these deoxyribozymes is enhanced when their substrate-binding arms include some locked nucleic acid (LNA) residues, but the mechanistic basis of this enhancement was not explored. Here we dissected the kinetics and thermodynamics underlying the reaction of LNA-containing 8–17 deoxyribozymes. Four 8–17 constructs were designed to target sequences within the E6 mRNA from human papillomavirus type 16. When one of these deoxyribozymes (DNAzymes) and the corresponding LNA-armed enzyme (LNAzyme) were tested against a minimal RNA substrate, they showed similar rates of substrate binding and similar rates of intramolecular cleavage, but the LNAzyme released its substrate more slowly. The superior thermodynamic stability of the LNAzyme-substrate complex led to improved performances in reactions carried out at low catalyst concentrations. The four DNAzymes and the corresponding LNAzymes were then tested against extended E6 transcripts (>500 nucleotides long). With these structured substrates, the LNAzymes retained full activity, whereas the DNAzymes cleaved extremely poorly, unless they were allowed to pre-anneal to their targets. These results imply that LNAzymes can easily overcome the kinetic barrier represented by local RNA structure and bind to folded targets with a faster association rate as compared with DNAzymes. Such faster annealing to structured targets can be explained by a model whereby LNA monomers favor the initial hybridization to short stretches of unpaired residues (“nucleation”), which precedes disruption of the local mRNA structure and completion of the binding process.

scholarly journals Structural and mechanistic basis of the high catalytic activity of monooxygenase Tet(X4) on tigecycline

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qipeng Cheng ◽  
Yanchu Cheung ◽  
Chenyu Liu ◽  
Qingjie Xiao ◽  
Bo Sun ◽  
...  
Keyword(s):  
Rational Design ◽  
Substrate Binding ◽  
Catalytic Efficiency ◽  
Binding Domain ◽  
Multiple Drug ◽  
High Catalytic Activity ◽  
Multiple Drug Resistant ◽  
Mechanistic Basis ◽  
Substrate Binding Domain ◽  
Fad Binding

Abstract Background Tigecycline is a tetracycline derivative that constitutes one of the last-resort antibiotics used clinically to treat infections caused by both multiple drug-resistant (MDR) Gram-negative and Gram-positive bacteria. Resistance to this drug is often caused by chromosome-encoding mechanisms including over-expression of efflux pumps and ribosome protection. However, a number of variants of the flavin adenine dinucleotide (FAD)-dependent monooxygenase TetX, such as Tet(X4), emerged in recent years as conferring resistance to tigecycline in strains of Enterobacteriaceae, Acinetobacter sp., Pseudomonas sp., and Empedobacter sp. To date, mechanistic details underlying the improvement of catalytic activities of new TetX enzymes are not available. Results In this study, we found that Tet(X4) exhibited higher affinity and catalytic efficiency toward tigecycline when compared to Tet(X2), resulting in the expression of phenotypic tigecycline resistance in E. coli strains bearing the tet(X4) gene. Comparison between the structures of Tet(X4) and Tet(X4)-tigecycline complex and those of Tet(X2) showed that they shared an identical FAD-binding site and that the FAD and tigecycline adopted similar conformation in the catalytic pocket. Although the amino acid changes in Tet(X4) are not pivotal residues for FAD binding and substrate recognition, such substitutions caused the refolding of several alpha helixes and beta sheets in the secondary structure of the substrate-binding domain of Tet(X4), resulting in the formation of a larger number of loops in the structure. These changes in turn render the substrate-binding domain of Tet(X4) more flexible and efficient in capturing substrate molecules, thereby improving catalytic efficiency. Conclusions Our works provide a better understanding of the molecular recognition of tigecycline by the TetX enzymes; these findings can help guide the rational design of the next-generation tetracycline antibiotics that can resist inactivation of the TetX variants.

Fibronexus-Like Adhesion Sites are Present at the Invasive Zones of Human Epidermoid Carcinomas

1982 ◽  
Vol 40 ◽  
pp. 106-109
Author(s):  
Irwin I. Singer
Keyword(s):  
Cell Cycle ◽  
Serum Concentration ◽  
Substrate Binding ◽  
High Serum ◽  
Adhesion Sites ◽  
Substrate Adhesion ◽  
Focal Contacts ◽  
Adhesion Complex ◽  
Low Serum

Our previous results indicate that two types of fibronectin-cytoskeletal associations may be formed at the fibroblast surface: dorsal matrixbinding fibronexuses generated in high serum (5% FBS) cultures, and ventral substrate-adhering units formed in low serum (0.3% FBS) cultures. The substrate-adhering fibronexus consists of at least vinculin (VN) and actin in its cytoplasmic leg, and fibronectin (FN) as one of its major extracellular components. This substrate-adhesion complex is localized in focal contacts, the sites of closest substratum approach visualized with interference reflection microscopy, which appear to be the major points of cell-tosubstrate adhesion. In fibroblasts, the latter substrate-binding complex is characteristic of cultures that are arrested at the G1 phase of the cell cycle due to the low serum concentration in their medium. These arrested fibroblasts are very well spread, flattened, and immobile.

Long-range electrostatic effects in biomolecular simulations

1997 ◽  
Vol 94 ◽  
pp. 1346-1364 ◽  
Author(s):  
TA Darden ◽  
A Toukmaji ◽  
LG Pedersen
Keyword(s):  
Long Range ◽  
Electrostatic Effects ◽  
Biomolecular Simulations

Taschenatlas Anatomie, Band 3: Nervensystem und Sinnesorgane

2018 ◽  
Author(s):  
Werner Kahle ◽  
Michael Frotscher ◽  
Frank Schmitz
Keyword(s):  
Band 3
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