Residue binding competitive. Medical search. Frequent questions

The structure reveals key active-site residues at the domain interface, including His200, Arg297 and Ser179 that are involved in catalysis and/or ligand binding and are highly conserved in TyrA proteins from all three kingdoms of life. (rcsb.org)
This conformational change brings the substrate, cofactor and active-site residues into close proximity for catalysis. (rcsb.org)
The key, conserved active site residues are well-defined in the structure and positioned appropriately to bind substrates, adenosine monophosphate and ribose-5-phosphate. (biomedcentral.com)

Thyroglobulin contains 2 subunits, which together contain 115 tyrosine residues, each of which is a potential site for iodination. (medscape.com)

Similar to endogenous ligands, HT1-0 needs hydrophobic and basic residues to bind hMC4R. (iric.ca)
For example, optimal peptides fitting into the murine MHC class I Db groove are 9 to 11 amino acids long and require as MHC anchor residues an Asn (N) at position 5 and also either a hydrophobic residue, a Met (M) or a Cys (C), at the carboxy terminus. (ox.ac.uk)
We find that lignin binds preferentially both to the elements of cellulose to which the cellulases also preferentially bind (the hydrophobic faces) and also to the specific residues on the cellulose-binding module of the cellulase that are critical for cellulose binding of Tr Cel7A (Y466, Y492, and Y493). (biomedcentral.com)

Indeed, SSRIs and TCAs bind in the extracellular vestibule of LeuT and act as non-competitive inhibitors of transport. (rcsb.org)
By contrast, multiple studies demonstrate that both TCAs and SSRIs are competitive inhibitors for eukaryotic BATs and bind to the primary binding pocket. (rcsb.org)
The chemically diverse inhibitors have a remarkably similar mode of binding in which they straddle transmembrane helix (TM) 3, wedge between TM3/TM8 and TM1/TM6, and lock the transporter in a sodium- and chloride-bound outward-facing open conformation. (rcsb.org)
Examples of a novel series of phenanthrolinones are shown to be potent competitive inhibitors of avian prolyl 4-hydroxylase, and of collagen hydroxylation, in embryonic chick tendon cells and human foreskin fibroblasts in vitro and in the oestradiol-stimulated rat uterus in vivo. (embl.de)
His main research topics have been the design, synthesis, and study of the binding modes of peptidoglycan biosynthetic pathway inhibitors. (degruyter.com)
Among the currently available options for the treatment of chronic myeloid leukemia (CML), ATP-competitive tyrosine kinases inhibitors (Gleevec ® , Dasatinib ® and Nilotinib ® ) represent one of the most promising therapeutic approaches developed in the last 10-15 years. (eurekaselect.com)
The T315I mutation at the gatekeeper residue is very frequent in advanced phases of the disease and is one of the main causes of resistance, disrupting important contact points between the inhibitors and the enzyme. (eurekaselect.com)
Different strategies have been implemented to overcome this resistance, such as the recent development of more selective non-ATP competitive inhibitors targeting sites outside the ATP-binding cleft. (eurekaselect.com)
The binding of these inhibitors blocks the Bcr-Abl kinase in the inactive conformation and provides an advantage in overcoming drug resistance due to kinase mutations. (eurekaselect.com)
Here we report potent and selective KDM5 covalent inhibitors designed to target cysteine residues only present in the KDM5 sub‐family. (chembiohub.com)
Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. (mdpi.com)
We were inspired by a series of publications emanating from the Jorgensen and Anderson groups describing the design of potent, non-peptidic, competitive SARS-CoV-2 M(pro) inhibitors, and we saw an opportunity to make several design modifications to improve the overall pharmacokinetic profile of these compounds without losing potency. (cdc.gov)
Several of the synthesized compounds proved to be potent, competitive M(pro) inhibitors with improved metabolic stability profiles. (cdc.gov)

The final LeuBAT mutant binds the SSRI sertraline with a binding constant of 18 nM and displays high-affinity binding to a range of SSRIs, SNRIs and a TCA. (rcsb.org)
For chemokines binding with high affinity to sugar residues, immobilization can even lead to the formation of stable solid phase gradients, which induce a variant of haptotaxis 9 . (nature.com)
After having captured antigen in non-lymphoid tissues, DCs migrate along immobilized gradients of the high affinity sugar-binding chemokine (C-C motif) ligand21 (CCL21) towards lymphatic vessels, from where they are flushed into the sinus of lymph nodes. (nature.com)
We then derived from the conotoxin the linear peptide HT1-0, a competitive antagonist of G s , G 15 , and β-arrestin2 pathways with a low nanomolar affinity for hMC4R. (iric.ca)
The scenery of pairwise proteinCprotein interfaces Drug-like substances typically exert their actions through binding to high-affinity sites of the proper shape and chemical composition. (gasyblog.com)
To identify the amino acids involved in the specific regulatory properties of glucokinase, and particularly its low affinity for glucose, mutants of the human islet enzyme have been prepared, in which glucokinase-specific residues have been replaced. (diabetesjournals.org)
As a rule, mutations changed the affinity for glucose and for the competitive inhibitor mannoheptulose (MH) in parallel, whereas they barely affected the affinity for N-acetylglucosamine (NAG). (diabetesjournals.org)
A small reduction in the affinity for the regulatory protein was observed with mutations of residues on the smaller domain and in the hinge region, confirming the bipartite nature of the binding site for the regulatory protein. (diabetesjournals.org)
Yet another study provides indicated that T790M also escalates the affinity of EGFR CPP32 for ATP, thus out-competing ATP-competitive TKIs and rebuilding enzymatic activity within their existence (7). (technuc.com)
By Db competitive binding analysis, only two of these 11 GP peptides and 1 of these 20 NP peptides bound to the MHC Db molecule with an affinity equivalent to the measured affinities for the three known GP1, GP2, and NP cytotoxic T-lymphocyte (CTL) epitopes. (ox.ac.uk)
The presence of the loop in the allosteric site may be an additional level of regulation, whereby low affinity molecules are precluded from binding. (biomedcentral.com)
In the first Abd technology application, we used a competitive surface plasmon resonance (cSPR) method [9] that depends on high affinity interaction of the antibody fragment with GTP-bound RAS. (cancer.gov)
Possible screening candidates must fulfill two fundamental requirements: They must (i) show an affinity to acetylcholinesterase well balanced between sufficient binding and competitive inhibition and (ii) facilitate the nucleophilic cleavage of the phosphorylated catalytic serine residue. (irb.hr)
It is also suspected that the cellulose-binding module (CBM) of cellulases participates in lignin binding, as enzymes containing a CBM have a higher affinity for lignin than those without one [ 20 , 22 ]. (biomedcentral.com)
These compounds were docked into the M(pro) active site and subsequently prioritized for synthesis based upon relative binding affinity values calculated by FEP+. (cdc.gov)
In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 receptors. (cdc.gov)

To further aid covalent drug design, we extended a functional group mapping approach based on explicit solvent all-atom molecular simulations (SILCS: site identification by ligand competitive saturation) that intrinsically considers protein flexibility, functional group, and protein desolvation along with functional group-protein interactions. (nih.gov)
These moieties are critical in terms of their role in in-vivo safety and efficacy (pharmacodynamics and pharmacokinetics), protein folding, protein targeting and trafficking, ligand binding, stability, protein halfâ life regulation, and immunogenicity (8). (chromatographyonline.com)
In one study of a large set of protein-ligand complexes, we tried to improve the free energies of binding by using MD simulations with QM-derived charges, which sometimes led to improved results, but not always. (lu.se)
We also ran QM/MM simulations on casein-kinase 2 (CK2), where the ligand and a few surrounding residues were treated at the QM level, and the rest of the system at the MM level. (lu.se)
Furthermore, it is important and challenging to accurately model the large entropic contribution to ligand-binding free energies. (lu.se)
Additionally, we compared how MD and grand-canonical Monte Carlo (GCMC) can be used to assess dynamics and thermodynamics of protein-ligand binding for both buried and solvent-exposed binding sites. (lu.se)

Furthermore, HinfPDH adopts a more closed conformation compared with TyrA proteins that do not have tyrosine bound. (rcsb.org)
in planning), systematically dealing with each proteins in turn simply because receptor and calculating the depth occupied by each residue using this program Ghecom (Kawabata, 2010). (gasyblog.com)
Cambinol Our primary data reveal that while protein-peptide connections make better general use of user interface surface area pockets on the proteins partners in comparison to various other classes of relationship (Fig.?3a), connections between two globular protein Cambinol often utilize deep relationship sites (Fig.?3b), only if with a little pocket installing an individual residue also. (gasyblog.com)
The ordinate procedures how deep the neighborhood pocket environment across the residue is certainly, assessed as the deepest partner proteins atom discovered within 5? (gasyblog.com)
The covalent binding to the targeted proteins was confirmed by MS and time‐dependent inhibition. (chembiohub.com)
We adopted a distinct approach aimed initially at interfering with protein-protein interactions of RAS, and other so-called undruggable targets like transcription factors, using molecular biology tools called intracellular antibodies that bind to target proteins inside cells. (cancer.gov)

Tyrosine is bound directly at the catalytic site, suggesting that it is a competitive inhibitor of HinfPDH. (rcsb.org)
The primary focus was on the 3-position of the enzyme and the production of two mutants, V3W and V3C, together with their analysis in terms of interfacial binding and catalytic activity. (soton.ac.uk)
Consequently, both the binding and the catalytic rate of DL-glyceraldehyde reduction depend on residue 299 in AKR1B10. (tam-receptor.com)

Due to a presence of =N-NH- fragment in its structure 1 forms hydrogen bonds with methionine and aspartic acid residues in the JNK ATP-binding pocket. (doaj.org)
The bulkier methionine residue at placement 790 sterically hinders binding of either gefitinib or erlotinib towards the ATP-binding pocket. (technuc.com)

REAGEN ™ Streptomycin ELISA Test Kit is a competitive enzyme immunoassay for the quantitative analysis of streptomycin and dihydrostreptomycin in feed, honey, kidney, liver, meat (beef, chicken and pork), milk, serum and urine. (elisatest-kits.com)
The Furaltadone (AMOZ) ELISA Kit is competitive ELISA for the qualitative or quantitative analysis of Furaltadone (AMOZ) in samples of poultry tissues, liver, eggs etc.Meizheng Bio-Tech Company Overview. (mzfoodtest.com)

To facilitate the design of this class of ligands, computational methods can be used to help identify reactive nucleophilic residues, frequently cysteines, on a target protein for covalent binding, to test various warhead groups for their potential reactivities, and to predict noncovalent contributions to binding that can facilitate drug-target interactions that are important for binding specificity. (nih.gov)

Competitive and noncompetitive phage enzyme linked immunosorbent assays (ELISAs) for benzothiostrobin were developed by using a clone C3-3 specific to the benzothiostrobin-free mAb and a clone N6-18 specific to the benzothiostrobin immunocomplex, respectively. (cdc.gov)
PD-L1 binding assays were performed using the transduced PD-L1-expressing lymphoma cell line U-698-M and wild-type U-698-M cells as a negative control. (snmjournals.org)
Additional competition assays show that compounds were non 2‐OG competitive. (chembiohub.com)
We exploited the specific binding of the antibody fragment and were able to identify RAS-binding compounds in antibody-competition assays (illustrated in Fig.1). (cancer.gov)
In competitive assays with wild-type cells, substitution of a heterologous V region impaired the survival of three ABC lines. (arizona.edu)

Dibenzo[cd,g]indazol-6(2H)-one (1) has been shown as a competitive JNK inhibitor and antiviral agent and was used in this work as a prototype. (doaj.org)

Under the optimal conditions, the half maximal inhibition concentration (IC50) of the competitive phage ELISA and the concentration of analyte producing 50% saturation of the signal (SC50) of the noncompetitive phage ELISA for benzothiostrobin were 0.94 and 2.27 ng mL(-1), respectively. (cdc.gov)
The reaction of the mutant AKR1B10 is definitely inhibited by fenofibric acid, but manifests genuine non-competitive inhibition kinetics that are different from those shown for the wild-type enzyme. (tam-receptor.com)

In addition to these two GP and one NP peptides, computer search revealed 11 other GP peptide sequences and 20 additional NP sequences that contained the Db binding motif. (ox.ac.uk)

The resulting color intensity, after addition of the HRP substrate (TMB), has an inverse relationship with the streptomycin residue concentration in the sample. (elisatest-kits.com)
Substrate specificity of AKR1B10 is definitely drastically affected by the mutation of the residue 299 from Cys to Ser. (tam-receptor.com)

Twenty-three phage-displayed peptides that specifically bind to an anti-benzothiostrobin monoclonal antibody (mAb) in the absence or presence of benzothiostrobin were isolated from a cyclic 8-residue peptide phage library. (cdc.gov)
Discriminated selection among viral peptides with the appropriate anchor residues: implications for the size of the cytotoxic T-lymphocyte repertoire and control of viral infection. (ox.ac.uk)
Structural characterization of peptides restricted by major histocompatibility complex (MHC) class I molecules has identified residues critical for MHC class I binding and for T-cell receptor recognition. (ox.ac.uk)

Furazolidone Test is used for testing Furazolidone residues in livestock, poultry and aquatic products, suitable for site rapid testing of all kinds of enterprises, testing agencies and supervision departments. (ballyabio.com)

this effect was additive to that previously observed for the E279Q mutant, indicating that the binding site for long-chain acyl CoAs is located on the upper face of the larger domain. (diabetesjournals.org)
The V3W mutant was prepared because the equivalent unique trytophan in the pancreatic enzyme has been extensively used as a natural probe for interfacial binding. (soton.ac.uk)
A final mutant, H48Q, was constructed to produce an inactive enzyme and provide an ideal interfacial binding protein for use in competitive binding studies. (soton.ac.uk)

25-OHD (25-hydroxyvitamin D), the major circulating metabolite of vitamin D, was measured in serum by competitive protein-binding (CPB) assay and radioimmunoassay kit (Nichols, San Juan Capistrano, California). (who.int)

Nitrofurans are metabolised in animal tissue to protein-bound residues. (europroxima.com)
CPC-IGF-1 remained bound within the tissue while unmodified IGF-1 cleared out. (biomedcentral.com)

The binding modes and interactions between rosmarinic acid and enolase were preliminary explored by molecular docking analysis. (biomedcentral.com)
Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. (cdc.gov)

The European Commission yesterday (25 February) ruled out binding EU-wide sustainability criteria for biomass, offering member states recommendations for national action instead. (forestindustries.eu)
The Commission's environment department, backed by a group of member states including the UK and the Netherlands, favoured binding sustainability criteria in order to ensure the environmental integrity of biomass energy production. (forestindustries.eu)
Biomass is one of the most important resources for reaching our renewable energy targets.It already contributes more than half of renewable energy consumption in the EU, providing a clean, secure and competitive energy resource," said Energy Commissioner Günther Oettinger. (forestindustries.eu)
But it argued that biomass waste and wood-processing residues are by-products that would be produced anyway, regardless of the energy sector. (forestindustries.eu)
Biomass, either solid or gaseous, is biological material that usually derives from agricultural crops and residues, from forestry, or from biodegradable waste such as municipal waste and sewage sludge. (forestindustries.eu)
What factors stand in the way for a global power transition to competitive, industrial-scale biomass conversion? (lu.se)

Finally, further experimental research studies are needed to evaluate the complex mechanisms by which lead may cause cancer with particular emphasis on the roles of oxidative stress / apoptosis and the roles of cellular defense mechanisms, signaling pathways and intracellular lead binding patterns in mediating these processes. (who.int)

If the streptomycin residue is present in the sample, it will compete for the streptomycin antibody, thereby preventing the streptomycin-HRP from binding to the antibody attached to the well. (elisatest-kits.com)
When the antibody fragment is bound to RAS, it serves as a competitor of compounds binding to the same region. (cancer.gov)

Traditional drugs interact with their target in a reversible equilibrium, while irreversible covalent drugs increase the drug-target interaction duration by forming a covalent bond with targeted residues and thus may offer a more effective therapeutic approach. (nih.gov)

Based on these factors, it seemed possible that compounds that bind to antigens could be selected using Dab binding sites and that these compounds would be surrogates of the Dab. (cancer.gov)
Thus, our Abd technology identified a hit chemical series interacting with a pocket [10, 11] near the effector binding region in RAS (activated pan-RAS binding compounds) [9]. (cancer.gov)
First that RAS is indeed druggable (as many labs have now shown, in particular KRASG12C binding compounds [13-15]) and that antibodies could indeed be used to guide the isolation of chemical matter with our Abd technology. (cancer.gov)

The noncompetitive phage ELISA showed higher selectivity compared to the competitive. (cdc.gov)
The EuroProxima AMOZ ELISA is a competitive enzyme immunoassay that is validated for screening of several food matrices. (europroxima.com)
The method is based on a competitive colorimetric ELISA assay. (elisatest-kits.com)
Veterinary Drug Residue ELISA Test Kits cover rapid testing kits and instruments, enabling rapid detection of Tetracyclines, Sulfonamides, Beta-lactam, Chloramphenicol, Lincomycin, Streptomycin, Quinolones, Gentamicin and so on by an indirect competitive ELISA techonology. (mzfoodtest.com)
Procedure Overview The method is based on a competitive, two-step colorimetric enzyme-linked immunosorbent assay (ELISA). (mzfoodtest.com)

The allosteric site is also relatively well conserved but, in the EcKPRS structure, several residues from a flexible loop occupy the site where the allosteric modulator, adenosine diphosphate, is predicted to bind. (biomedcentral.com)

We further optimized the sequence to include hydrophilic asparagine (N) spacers (CPC +14N, (RRRR(NNRRR) 3 R) to minimize its competitive binding within the synovial fluid (SF) and enhance its cartilage targeting property (Fig. 1 A). (biomedcentral.com)

The addition of a precursor 13-residue oligosaccharide moiety GlcNAc2Man8Gluc3 to the nascent polypeptide chain occurs in the endoplasmic reticulum, following which the assembly folds and acquires its secondary, tertiary, and quaternary structure. (chromatographyonline.com)

Amiloride acted primarily as a competitive antagonist, reducing the sensitivity of the receptor to GABA without affecting the maximal current amplitude. (aspetjournals.org)
We discovered a novel intermediary conformation where the mvACE2 receptor is bound to the receptor-binding domain (RBD) of the S glycoprotein in a 'down' position, approximately 34° lower than previously reported 'up' RBD. (cdc.gov)

Analyses of PPI interfaces using brand-new computational equipment can identify crucial residues in interfaces mediating the proteinCprotein relationship (Pires et?al. (gasyblog.com)
One crucial property that is not yet competitive for Fe carbene photosensitisers is how long they stay in the excited state, i.e. their lifetime. (lu.se)

Each true point represents a residue contributed with the shortest chains in each interface pair. (gasyblog.com)

From a Cone Snail Toxin to a Competitive MC4R Antagonist. (iric.ca)

A cooperative and competitive interaction between multiple enzymes, cell lines, and cell culture conditions causes processing of the oligosaccharide structure during which some of the already attached moieties like mannose are trimmed to yield a fiveâ residue core (Man3GlcNAc2), to which N-acetylglucosamine (GlcNAc), fucose, galactose, and N-acetylneuraminic acid (sialic acid or Neu5Ac) residues get added in a probabilistic fashion. (chromatographyonline.com)
In drug discovery, it is of utmost importance to accurately calculate the free energies of binding ligands to various protein targets, such as enzymes and receptors. (lu.se)

Despite evidence suggesting that in vivo chemokines are often immobilized to sugar residues, limited information is available how cells respond to immobilized chemokines. (nature.com)
Ubiquitylation of H2AK15 by RNF168 inhibits chromatin acetylation by TIP60, while this residue can be acetylated by TIP60 in vivo, blocking its ubiquitylation. (houstonmethodist.org)

2004) and/or are potential fragment binding sites (Jubb et?al. (gasyblog.com)

Such magnetic relaxation dispersion (MRD1) structural polymorphism of quadruplexes ( 2, 5, 6 ), but little measurements have been used to study ion binding (via 23Na is known about the energetics and kinetics of ion binding. (lu.se)

The results highlight the potential importance of interfacial trytophan residues in promoting the penetration of condensed zwitterionic interfaces as also seen with the surface monolayer of cell membranes. (soton.ac.uk)

Altogether, these results uncover an intricate mechanism orchestrated by the TIP60 complex to regulate 53BP1-dependent repair through competitive bivalent binding and modification of chromatin. (houstonmethodist.org)

Here we engineered LeuT to harbour human BAT-like pharmacology by mutating key residues around the primary binding pocket. (rcsb.org)
Not JNK but some other kinase with the similar structure of the ATP-binding pocket is the most likely target of 3. (doaj.org)
The chemical compound series that was developed in this work is a pan-RAS series binding to all the RAS isoforms [12] because the binding pocket is found in KRAS, HRAS and NRAS. (cancer.gov)

Differential migratory patterns illustrate the potential of our setup to quantitatively study the competitive response to both types of gradients. (nature.com)

Open up in another home window Fig.?3 Residue binding settings at pairwise PPI interfaces. (gasyblog.com)

An ionic network consisting of Arg297 (a key residue for tyrosine binding), a water molecule, Asp206 (from the loop between β5 and β6) and Arg365' (from the additional C-terminal helix of the adjacent monomer) is observed that might be involved in gating the active site. (rcsb.org)
Ghecom procedures the tiniest probe size that cannot enter a cavity (Rinaccess), being a per-residue way of measuring depth of formation or occupation of the binding site. (gasyblog.com)
These and other results suggest that NAG and MH bind to the same site but to different conformations of glucokinase. (diabetesjournals.org)

2014) and potential binding sites (Hendlich et?al. (gasyblog.com)

Stimulated by the pioneering studies on the cationic porphyrin TMPyP4 and the natural product telomestatin, follow-up studies have developed, rapidly leading to a large diversity of macrocyclic structures with remarkable-quadruplex binding properties and biological activities. (hindawi.com)
In this review we summarize the current state of the art in detailing the three main categories of quadruplex-binding macrocycles described so far (telomestatin-like polyheteroarenes, porphyrins and derivatives, polyammonium cyclophanes), and in addressing both synthetic issues and biological aspects. (hindawi.com)

In this work, we use both approaches to study drug-albumin binding and support the results by comparison with other complementary techniques and by structural and computational analysis. (mdpi.com)

We likened segmentation (binding epitope continuity), solvent Cambinol availability, secondary framework, interatomic connections and binding depth (Jubb et?al. (gasyblog.com)

HinfPDH is a dimeric enzyme, with each monomer consisting of an N-terminal α/β dinucleotide-binding domain and a C-terminal α-helical dimerization domain. (rcsb.org)

High and specific binding of 68 Ga-BMS-986192 to human PD-L1-expressing cancer cells was confirmed, which closely correlates with the respective PD-L1 expression level determined by flow cytometry and immunohistochemistry staining. (snmjournals.org)

The viability of one V H 4-34 + ABC line and the ability of its BCR to bind to its own cell surface depended on V region residues that mediate the intrinsic autoreactivity of V H 4-34 to self-glycoproteins. (arizona.edu)

Indeed, given that four guanine residues can self-associate in a planar arrangement through a Hoogsteen-type hydrogen-bonding network [ 4 ] to form a structure called G-quartet, G-rich strands can adopt a peculiar three-dimensional arrangement called G-quadruplex DNA [ 5 - 9 ] resulting from the stacking of several contiguous G-quartets (Figure 1 ). (hindawi.com)

Anatomy10

Organisms11

Chemicals and Drugs109

Analytical, Diagnostic and Therapeutic Techniques and Equipment46

Phenomena and Processes79

Disciplines and Occupations3

Technology, Industry, Agriculture1

Information Science9

Health Care4

Active-site residues3

Tyrosine residues1

Hydrophobic3

Inhibitors13

Affinity16

Ligand6

Proteins6

Catalytic3

Methionine2

Quantitative analysis2

Nucleophilic1

Assays5

Inhibitor1

Inhibition2

Motif1

Substrate2

Peptides3

Poultry1

Mutant3

Metabolite1

Tissue2

Interactions2

Biomass6

Intracellular1

Antibody2

Covalent1

Compounds3

ELISA5

Allosteric1

Sequence1

Polypeptide1

Receptor2

Crucial2

Chains1

Antagonist1

Enzymes2

Vivo2

Fragment1

Kinetics1

Penetration1

Modification1

Pocket3

Quantitatively1

Interfaces1

Site3

Sites1

Biological2

Study1

Secondary1

Domain1

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Region1

Structure1