Search results for "binding site"
showing 10 items of 856 documents
Drug Binding Properties of Tyrosine-Modified Human Serum Albumin
1978
Human serum albumin (HSA) has only a small number of specific binding sites for drugs. There are facts indicating that tyrosine residues may be involved in these binding sites. Thus we modified HSA with tetranitromethan, a reagent specific for tyrosine residues in proteins. As derived from an UV-absorption quotient three albumins with a degree of modification of two, five and eight residues per molecule were obtained. Only for the albumin with eight residues modified a small reduction of ordered secondary structure was found.
Theoretical studies of HIV-1 reverse transcriptase inhibition
2012
Computational methods for accurately calculating the binding affinity of a ligand for a protein play a pivotal role in rational drug design. We herein present a theoretical study of the binding of five different ligands to one of the proteins responsible for the human immunodeficiency virus type 1 (HIV-1) cycle replication; the HIV-1 reverse transcriptase (RT). Two types of approaches are used based on molecular dynamics (MD) simulations within hybrid QM/MM potentials: the alchemical free energy perturbation method, FEP, and the pathway method, in which the ligand is physically pulled away from the binding site, thus rendering a potential of mean force (PMF) for the binding process. Our com…
Metal specificity of the Ni(II) and Zn(II) binding sites of the N-terminal and G-domain of E. coli HypB
2021
HypB is one of the chaperones required for proper nickel insertion into [NiFe]-hydrogenase. Escherichia coli HypB has two potential Ni(II) and Zn(II) binding sites—the N-terminal one and the so-called GTPase one. The metal-loaded HypB–SlyD metallochaperone complex activates nickel release from the N-terminal HypB site. In this work, we focus on the metal selectivity of the two HypB metal binding sites and show that (i) the N-terminal region binds Zn(II) and Ni(II) ions with higher affinity than the G-domain and (ii) the lower affinity G domain binds Zn(II) more effectively than Ni(II). In addition, the high affinity N-terminal domain, both in water and membrane mimicking SDS solution, has a…
Characterization of DrosophilaHemoglobin
2002
In contrast to previous assumptions, the fruit fly Drosophila melanogaster possesses hemoglobin. This respiratory protein forms a monomer of about 17 kDa that is not exported into the hemolymph. Recombinant Drosophila hemoglobin displays a typical hexacoordinated deoxy spectrum and binds oxygen with an affinity of 0.12 torr. Four different hemoglobin transcripts have been identified, which are generated by two distinct promoters of the hemoglobin (glob1) gene but are identical in their coding regions. Putative binding sites for hypoxia-regulated transcription factors have been identified in the gene. Hemoglobin synthesis in Drosophila is mainly associated with the tracheal system and the fa…
Design, Synthesis and Biological Evaluation of Novel Pyrazolo[1,2,4]triazolopyrimidine Derivatives as Potential Anticancer Agents
2021
Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations…
How To Design Selective Ligands for Highly Conserved Binding Sites: A Case Study Using N-Myristoyltransferases as a Model System
2019
A model system of two related enzymes with conserved binding sites, namely N-myristoyltransferase from two different organisms, was studied to decipher the driving forces that lead to selective inhibition in such cases. Using a combination of computational and experimental tools, two different selectivity-determining features were identified. For some ligands, a change in side-chain flexibility appears to be responsible for selective inhibition. Remarkably, this was observed for residues orienting their side chains away from the ligands. For other ligands, selectivity is caused by interfering with a water molecule that binds more strongly to the off-target than to the target. On the basis o…
Evidence for essential primary amino groups in a bacterial coupling factor F1ATPase.
1980
Abstract We have found that the binding of pyridoxal-5′-phosphate to 6 primary amino groups leads to the inactivation of the enzyme. A preferential reaction of pyridoxal-5′-phosphate with the α-subunits of this enzyme can be demonstrated. The reactivity of the amino groups is influenced by various effectors. In the presence of ATP the inhibition of the ATPase activity is noncompetitive.
Covalent modificaition of juvenile hormone binding proteins by photoaffinity labeling: An unexpected gel shift effect
1994
The 32 kD juvenile hormone binding protein (JHBP) and two 80 kD proteins in larval Manduca sexta hemolymph were labeled with [3H]FDK, a photoaffinity analog of methyl farnesoate (MF). The labeling could be completely displaced by a 30-fold excess of either MF or JH II, demonstrating that [3H]FDK binds specifically to the JH binding sites of the 32 kD JHBP and the 80 kD proteins. In addition, a high molecular-mass protein was labeled with [3H]FDK; labeling could be displaced by excess MF but not by JH II, demonstrating the selectivity in binding MF. The 32 kD JHBP also appeared to weakly bind the potent juvenoid, methoprene, at the JH binding site. Covalent modification by [3H]FDK induced a …
The NreA Protein Functions as a Nitrate Receptor in the Staphylococcal Nitrate Regulation System
2013
Staphylococci are able to use nitrate as an alternative electron acceptor during anaerobic respiration. The regulation of energy metabolism is dependent on the presence of oxygen and nitrate. Under anaerobic conditions, staphylococci employ the nitrate regulatory element (Nre) for transcriptional activation of genes involved in reduction and transport of nitrate and nitrite. Of the three proteins that constitute the Nre system, NreB has been characterized as an oxygen sensor kinase and NreC has been characterized as its cognate response regulator. Here, we present structural and functional data that establish NreA as a new type of nitrate receptor. The structure of NreA with bound nitrate w…
Azacoronands and Azacyclophanes
2012
Azacycloalkanes and azacyclophanes are among the first macrocyclic ligands developed in the field of supramolecular chemistry. Since they are polyamines, they show dual nature in the coordination of both metal cations, when they are in the free-base form, and anionic species, when they are protonated. As a matter of fact, they played a key role in the birth of macrocyclic chemistry of transition metal complexes and anion coordination chemistry. Furthermore, azacyclophanes fostered also the birth of apolar complexation in aqueous solution, since their aromatic units act as binding sites for apolar substrates. Keywords: azacycloalkanes; azacyclophanes; metal complexes; anion complexes; apolar…