Disease relevance of Binding Sites

• Of considerable interest is the recent discovery that some chemokines function as HIV-suppressive factors by interacting with chemokine receptors which, together with CD4, were recognized as the binding sites for HIV-1 [1].
• Genetic analysis of monoclonal antibody and HIV binding sites on the human lymphocyte antigen CD4 [2].
• The 434 repressor and cro protein each bind to three similar sites in the rightward phage 434 operator, OR, and they make different contacts in each binding site, as revealed by the chemical probe dimethyl sulfate [3].
• The interaction of the TATA factor on the adenovirus E4 promoter with GAL4 binding sites adjacent to the TATA site was qualitatively altered in response to GAL4 binding [4].
• Lactose, known to block the binding site on the ricin B subunit, protected ricin from NAI modification of binding or toxicity [5].

Psychiatry related information on Binding Sites

• Binding sites for tritum-labeled gamma-aminobutyric acid (GABA) in cerebellar cortex of Huntington's chorea patients have an increased affinity but unaltered maximum capacity as compared to binding sites in tissue from control patients [6].
• 7-Methylinosine, which does not bind to the brain benzodiazepine binding site in vitro, had no effect on the diazepam-induced increase in exploratory behavior [7].
• RESULTS: The major finding was that there is a global reduction in benzodiazepine site binding throughout the brain in patients with panic disorder compared with controls [8].
• Since the diazepam-induced increase of [3H]muscimol binding is paralleled by a significant potentiation of the inhibitory effect of muscimol on locomotor activity, it is proposed that the facilitatory action on GABAergic transmission elicited in vivo by diazepam is mediated by an increase in the Bmax of the binding sites of GABAA receptors [9].
• Two sequence changes in DYX1C1, one involving the translation initiation sequence and an Elk-1 transcription factor binding site (-3G --> A) and a codon (1249G --> T), introducing a premature stop codon and truncating the predicted protein by 4 aa, associate alone and in combination with dyslexia [10].

High impact information on Binding Sites

• This suggests a model of the RAG protein active site in which two divalent metal ions serve alternating and opposite roles as activators of attacking hydroxyl groups and stabilizers of oxyanion leaving groups [11].
• TRX is a small multifunctional protein that has a redox-active disulfide/dithiol within the conserved active site sequence: Cys-Gly-Pro-Cys [12].
• The degenerate binding indicated that the binding site of MHC proteins must have a significant number of conserved features [13].
• These binding sites are insensitive to the effects of guanine nucleotides and appear to be rapidly internalized [14].
• Prolyl hydroxylation generates a binding site for a ubiquitin ligase complex containing the von Hippel-Lindau (VHL) tumor suppressor protein, which results in HIFalpha destruction [15].

Chemical compound and disease context of Binding Sites

• Congenital myoclonus is a widespread neurologic disorder characterized by hyperexcitability, muscular spasticity and myoclonus associated with marked reduction in neural glycine binding sites [16].
• The finding that one chemokine receptor can function as a primary viral receptor strongly suggests that the HIV envelope glycoprotein contains a binding site for these proteins and that differences in the affinity and/or the availability of this site can extend the host range of these viruses to include a number of CD4-negative cell types [17].
• Previously, we localized the binding sites of LFA-1 and the major group of human rhinoviruses to the first NH2-terminal immunoglobulin-like domain of ICAM-1 [18].
• In this study we have used site-directed mutagenesis of this enzyme expressed in Escherichia coli to reveal several important functional regions of the protein including putative components of the triphosphate binding site and pyrophosphate exchange sites [19].
• Here we present a 2.2 A crystal structure of the replicative DNA polymerase from bacteriophage T7 complexed with a primer-template and a nucleoside triphosphate in the polymerase active site [20].

Biological context of Binding Sites

• Phosphorylation of tyrosine residues modulates enzymatic activity and creates binding sites for the recruitment of downstream signaling proteins [21].
• A GTPase-activating protein probably binds to and stabilizes the conformation of its cognate G protein that recognizes the transition state for hydrolysis, and may insert a catalytic residue into the G protein active site [22].
• It is a heterodimeric protein consisting of a catalytic subunit calcineurin A, which contains an active site dinuclear metal center, and a tightly associated, myristoylated, Ca(2+)-binding subunit, calcineurin B. The primary sequence of both subunits and heterodimeric quaternary structure is highly conserved from yeast to mammals [23].
• The cis-regulatory region of the proapoptotic gene reaper contains a radiation-inducible enhancer that includes a consensus p53 binding site [24].
• This promoter region lies directly adjacent to the third T antigen binding site but does not include that "TATA" sequence [25].

Anatomical context of Binding Sites

• The finding that phosphatidylserine directly binds to VSV and inhibits VSV attachment and infectivity suggests that plasma membrane phosphatidylserine could function as a binding site or portion of a binding site for VSV [26].
• Direct evidence for the existence of nominal antigen binding sites on T cell surface Ti alpha-beta heterodimers of MHC-restricted T cell clones [27].
• A critical virus-inducible element of this gene, PRDII, behaves interchangeably with the NF-kappa B binding site from the Ig kappa enhancer in both B lymphocytes and virus-infected fibroblasts [28].
• The crystal structures of an expressed vertebrate smooth muscle myosin motor domain (MD) and a motor domain-essential light chain (ELC) complex (MDE), both with a transition state analog (MgADP x AIF4-) in the active site, have been determined to 2.9 A and 3.5 A resolution, respectively [29].
• To distinguish between antibody titers and antibody activity, we measured the ability of serum immunoglobulin from 49 patients to induce accelerated degradation or blockade of the binding sites of acetylcholine receptors, using a mammalian skeletal-muscle tissue-culture system [30].

Associations of Binding Sites with chemical compounds

• Protein tyrosine phosphatases (PTPs) are a diverse group of enzymes that contain a highly conserved active site motif, Cys-x5-Arg (Cx5R) [31].
• The three-dimensional structures of tryptophan synthase, carbamoyl phosphate synthetase, glutamine phosphoribosylpyrophosphate amidotransferase, and asparagine synthetase have revealed the relative locations of multiple active sites within these proteins [32].
• Order out of chaos: assembly of ligand binding sites in heparan sulfate [33].
• The 20S (700-kDa) proteasome contains multiple peptidase activities that function through a new type of proteolytic mechanism involving a threonine active site [34].
• The available crystallographic structures for members of these families are discussed within the framework of the active site structure and catalytic mechanisms of molybdenum-cofactor-containing enzymes [35].

Gene context of Binding Sites

• The CETP contains binding sites for cholesteryl ester and triglycerides and probably acts by a carrier-mediated mechanism [36].
• Our results suggest that RAP1 may be a transcriptional regulator that can play a role in either repression or activation of transcription, depending upon the context of its binding site [37].
• Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP [38].
• Stimulation depended upon GAL4 binding sites inserted in the template [39].
• Highly conserved FGF-D2 and FGF-linker (between D2-D3) interfaces define a general binding site for all FGF-FGFR complexes [40].

Analytical, diagnostic and therapeutic context of Binding Sites

• Site-specific mutagenesis of this binding site prevents TPA induction and trans-activation by Jun/AP-1 [41].
• In each of the three resistant clones tested, there is an increase in the number of aspartate transcarbamylase active sites, determined by titration with 3H-PALA, which closely parallels the increase in enzyme activity [42].
• Here we have studied binding sites for rat atrial natriuretic peptide(6-33) (rANP) and AII in the brains of spontaneously (genetic) hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY) rats, by quantitative autoradiography [43].
• We report here that the circular dichroism (CD) spectrum of a synthetic 54-bp deoxyoligonucleotide corresponding to the TFIIIA binding site is similar to the CD spectrum of B-form DNA in solution [44].
• Here we use a DNA-crosslinking/immunoprecipitation assay to study in living cells the first step in the assembly of the preinitiation complex, the interaction between the TATA-box-binding protein (TBP) and its binding site, the TATA box [45].

References