Homology modeling of 3D structure of human chitinase-like protein CHI3L2

2010 ◽  
Vol 5 (4) ◽  
pp. 407-420 ◽  
Author(s):  
Anton Iershov ◽  
Konstantin Odynets ◽  
Alexander Kornelyuk ◽  
Vadim Kavsan
Keyword(s):  
Ligand Binding ◽  
Homology Modeling ◽  
3D Structure ◽  
Data Bank ◽  
Amino Acid Residues ◽  
Glycosyl Hydrolases ◽  
Structural Comparison ◽  
Quality Model ◽  
Homologous Proteins ◽  
Binding Groove

AbstractThe human genome encodes six proteins of family 18 glycosyl hydrolases, two active chitinases and four chitinase-like lectins (chi-lectins) lacking catalytic activity. The present article is dedicated to homology modeling of 3D structure of human chitinase 3-like 2 protein (CHI3L2), which is overexpressed in glial brain tumors, and its structural comparison with homologous chi-lectin CHI3L1. Two crystal structures of CHI3L1 in free state (Protein Data Bank codes 1HJX and 1NWR) were used as structural templates for the homology modeling by Modeller 9.7 program, and the best quality model structure was selected from the obtained model ensemble. Analysis of potential oligosaccharide-binding groove structures of CHI3L1 and CHI3L2 revealed significant differences between these two homologous proteins. 8 of 19 amino acid residues important for ligand binding are substituted in CHI3L2: Tyr34/Asp39, Trp69/Lys74, Trp71/Lys76, Trp99/Tyr104, Asn100/Leu105, Met204/Leu210, Tyr206/Phe212 and Arg263/His271. The differences between these residues could influence the structure of the ligand-binding groove and substantially change the ability of CHI3L2 to bind oligosaccharide ligands.

scholarly journals Homology Modeling and Prediction of Catalytic Amino Acid in the Neurotoxin from Indian Cobra (Naja naja)

2008 ◽  
Vol 2 (1) ◽  
pp. 97-102 ◽  
Author(s):  
Pallavi Somvanshi ◽  
Vijai Singh
Keyword(s):  
Amino Acid ◽  
Homology Modeling ◽  
Active Site ◽  
3D Structure ◽  
Nerve Impulse ◽  
Amino Acid Residues ◽  
Small Peptide ◽  
Naja Naja ◽  
Modeling And Prediction ◽  
Catalytic Amino Acid

The neurotoxin secreted by Indian cobra (Naja naja) binds to acetylcholine receptor of nerve cells, which leads to a lump in the nerve impulse, ceases breathing, thereby causing the death of a person due to suffocation. These neurotoxins are small peptide with approximately 7 kDa. Homology modeling was performed to generate the 3D structure of neurotoxins (A, B, C and D) of N. naja, using the known protein template crystal structure (PDB: 2CTX). The validation of 3D structure was done using PROCHECK. Furthermore, the prediction of catalytic amino acid residues in the active site domain of the 3-D structure of neurotoxin was identified. The 3-D structures of neurotoxin and catalytic amino acid residue may be used to target and design the antivenom drugs against the Indian cobra.

Protein modeling by homology using the example of tick-borne encephalitis serine protease NS3

2020 ◽  
pp. 59-66
Author(s):  
Nikita Ilment ◽  
Ekaterina Zinina
Keyword(s):  
Electron Microscopy ◽  
Homology Modeling ◽  
Homology Modelling ◽  
Protein Structures ◽  
3D Structure ◽  
Free Software ◽  
Homologous Proteins ◽  
Cryo Electron Microscopy ◽  
Tick Borne Encephalitis ◽  
Sequences Analysis

Homology modeling is a process of obtaining a 3D structure of a protein using various algorithms based on already known structures of homologous proteins. The spatial structure of protein is required for in silico protein evaluation. 3D structures can be obtained using different methods: NMR, Xray crystallography (XRC), and cryo-electron microscopy (cryo-EM), but these methods require a lot of time and money. At the same time, the speed of nucleotide sequences analysis is increasing, thereby creating a mismatch between the number of decoded genomes and the investigated 3D protein structures that are encoded by these sequences. Also, homology modeling is the easiest and fastest way to obtain the model of the desired protein. This review describes free software for homology modelling — SWISS-MODEL and MODELLER, how to use it and how to evaluate the results.

scholarly journals In SilicoDetermination and Validation of Baumannii Acinetobactin Utilization A Structure and Ligand Binding Site

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Fatemeh Sefid ◽  
Iraj Rasooli ◽  
Abolfazl Jahangiri
Keyword(s):  
Ligand Binding ◽  
Homology Modeling ◽  
Binding Sites ◽  
Tertiary Structure ◽  
Outer Membrane Proteins ◽  
3D Structure ◽  
Essential Element ◽  
Nosocomial Pathogen ◽  
Ligand Binding Sites

Acinetobacter baumanniiis a deadly nosocomial pathogen. Iron is an essential element for the pathogen. Under iron-restricted conditions, the bacterium expresses iron-regulated outer membrane proteins (IROMPs). Baumannii acinetobactin utilization (BauA) is the most important member of IROMPs inA. baumannii. Determination of its tertiary structure could help deduction of its functions and its interactions with ligands. The present study unveils BauA 3D structure viain silicoapproaches. Apart fromab initio, other rational methods such as homology modeling and threading were invoked to achieve the purpose. For homology modeling, BLAST was run on the sequence in order to find the best template. The template was then served to model the 3D structure. All the models built were evaluated qualitatively. The best model predicted by LOMETS was selected for analyses. Refinement of 3D structure as well as determination of its clefts and ligand binding sites was carried out on the structure. In contrast to the typical trimeric arrangement found in porins, BauA is monomeric. The barrel is formed by 22 antiparallel transmembraneβ-strands. There are short periplasmic turns and longer surface-located loops. An N-terminal domain referred to either as the cork, the plug, or the hatch domain occludes theβ-barrel.

scholarly journals Homology modeling of actin protein in Leishmania donovani and in silico prediction of active drugs

2020 ◽  
Vol 2 ◽  
pp. 52-57
Author(s):  
Dimpal Rani Bansal ◽  
Hanumanthrao Chandershekar Patil ◽  
Rajesh Kumari Patil
Keyword(s):  
Homology Modeling ◽  
Binding Affinity ◽  
In Silico ◽  
Structure Prediction ◽  
Leishmania Donovani ◽  
Secondary Structure Prediction ◽  
3D Structure ◽  
Data Bank ◽  
Discovery Studio ◽  
Actin Protein

Objectives: Leishmaniasis is a disease caused by leishmania parasite which is genus of trypanosome protozoa. Leishmania donovani promastigote inhibits biogenesis of phagolysosome due to the accumulation of periphagosomal F-actin. This inhibition of phagosome maturation gives favorable environment for differentiation of promastigote-to-amastigote and causes disease progression. L. donovani actin (LdACT) has been found to have unconventional biochemical behavior due to the different amino acid region in its sequence suggesting that it must have a three-dimensional (3D) structure different from eukaryotic actins making it a more specific for predication of antileishmanial drugs which is main objective of this study. Material and Methods: For carrying out this study, protein sequence was retrieved from the database SWISSPROT, analyzed by BIOEDIT software followed by primary and secondary structure prediction by PROTPARAM and SOPMA. A 3D structure of same was constructed by homology modeling using the yeast actin-human gelsolin segment 1 complex (protein data bank [PDB] ID:1yag) as a template with the help of Swiss model. The final model obtained was further accessed by PROCHECK and VERIFY 3D software which ensured the reliability of the model. This model of actin protein was further used for screening different chemical compounds with high binding affinity by GOLD and DISCOVERY STUDIO. Results: The results give information about the some inhibitors having highest binding affinity to the actin protein. Conclusion: This study will be useful for the development of pharmacophore models for in silico predication of active drugs as a part of antileishmanial drug therapy.

scholarly journals Insilico Characterization, Phylogenetic Analysis and Homology based 3D Structural Modeling of HSPA4 Heat Shock Protein Family a (Hsp70) Member 4 from Homo Sapiens (Human).

2019 ◽  
Vol 9 (1) ◽  
pp. 3086-3091
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Homology Modeling ◽  
Structure Prediction ◽  
Homo Sapiens ◽  
3D Structure ◽  
Protein Family ◽  
Template Molecule ◽  
Hsp 70 ◽  
Homologous Proteins

HSP70 are the specialized Heat Shock Proteins that show their novelty presence inside the deepest part of Cellular Component Networks of Chaperons and involve with various heat Shock repairing up mechanisms as main Catalytic Components. They actively participate in proper alignment and resistance of all types pressures by their proper dealing with substrates and proper exposure of their hydrophobic peptide portions inside of their substrate molecules. The exchange of information cum process of information occurs between the cell components through HSP70’s low level of affinity ATP bind sites and High Affinity level of ADP binding sites. Therefore, ATP hydrolysis process plays a key role in fundamental mechanisms, in vitro and as well as in in vivo repairing mechanisms for the functioning of Chaperone like functionalities of HSP 70 proteins. In the current study analysis, Homology Modeling methods permits us for modeling the 3D structure of the protein by taking backbone of experimentally determined 3D-Structures of homologous proteins extracted in various structural formats like PDBs. We worked with HSPA4 heat shock protein family A (HSP 70) part 4 from Homo sapiens ( Human ) and conducted 3-D structure prediction using an Automated Swiss Model Generation by employing the crystal structures of Template molecule. PDB Blast and Template search for required protein were conducted with help of all the parameters with respect to Imapact and Psi Impact angles and that leads to for most noteworthy sequence identity, structural alignments and functionalities. Finally, the homology modeling were performed by using SWISS modeler and modeled proteins were fine tuned by using the Ramachandran Plot, by using PROCHECK and 3D-Check Software Programs.

scholarly journals Androgen Receptor Ligand-Binding Domain Interaction and Nuclear Receptor Specificity of FXXLF and LXXLL Motifs as Determined by L/F Swapping

2006 ◽  
Vol 20 (8) ◽  
pp. 1742-1755 ◽  
Author(s):  
Hendrikus J. Dubbink ◽  
Remko Hersmus ◽  
Ashley C. W. Pike ◽  
Michel Molier ◽  
Albert O. Brinkmann ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Ligand Binding ◽  
Nuclear Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Amino Acid Residues ◽  
Systematic Analysis ◽  
Core Motif ◽  
Charged Residues ◽  
Binding Groove

Abstract The androgen receptor (AR) ligand-binding domain (LBD) binds FXXLF motifs, present in the AR N-terminal domain and AR-specific cofactors, and some LXXLL motifs of nuclear receptor coactivators. We demonstrated that in the context of the AR FXXLF motif many different amino acid residues at positions +2 and +3 are compatible with strong AR LBD interaction, although a preference for E at +2 and K or R at +3 was found. Pairwise systematic analysis of F/L swaps at +1 and +5 in FXXLF and LXXLL motifs showed: 1) F to L substitutions in natural FXXLF motifs abolished AR LBD interaction; 2) binding of interacting LXXLL motifs was unchanged or increased upon L to F substitutions; 3) certain noninteracting LXXLL motifs became strongly AR-interacting FXXLF motifs; whereas 4) other nonbinders remained unaffected by L to F substitutions. All FXXLF motifs, but not the corresponding LXXLL motifs, displayed a strong preference for AR LBD. Progesterone receptor LBD interacted with some FXXLF motifs, albeit always less efficiently than corresponding LXXLL motifs. AR LBD interaction of most FXXLF and LXXLL peptides depended on classical charge clamp residue K720, whereas E897 was less important. Other charged residues lining the AR coactivator-binding groove, K717 and R726, modulated optimal peptide binding. Interestingly, these four charged residues affected binding of individual peptides independent of an F or L at +1 and +5 in swap experiments. In conclusion, F residues determine strong and selective peptide interactions with AR. Sequences flanking the core motif determine the specific mode of FXXLF and LXXLL interactions.

The 3D structure of the defense-related rice protein Pir7b predicted by homology modeling and ligand binding studies

2008 ◽  
Vol 14 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Quan Luo ◽  
Wei-Wei Han ◽  
Yi-Han Zhou ◽  
Yuan Yao ◽  
Ze-Sheng Li
Keyword(s):  
Ligand Binding ◽  
Homology Modeling ◽  
3D Structure ◽  
Binding Studies ◽  
Rice Protein

In Silico Prediction and Validation of Oxygen-Regulated Protein N-myc Downstream Regulated Gene 3 and Virtual Screening of Competitive Inhibitors of L-Lactate as Therapeutics

2019 ◽  
Vol 16 (6) ◽  
pp. 637-644
Author(s):  
Hongyu Cao ◽  
Yanhua Wu ◽  
Xingzhi Zhou ◽  
Xuefang Zheng ◽  
Ge Jiang
Keyword(s):  
Active Sites ◽  
Competitive Inhibition ◽  
Hydrophobic Effect ◽  
3D Structure ◽  
Amino Acid Residues ◽  
In Silico Prediction ◽  
Hypoxic Response ◽  
Drug Candidates ◽  
Competitive Inhibitors ◽  
Extracellular Regulated Protein Kinases

Background: N-myc downstream regulated gene 3 (NDRG3) is a newly discovered oxygen-regulated protein which will bind with L-Lactate in hypoxia and further activate Raf (rapidly accelerated fibrosarcoma)-ERK (extracellular regulated protein kinases) pathway, promoting cell growth and angiogenesis. Methods: Competitive inhibition on the binding of NDRG3 and L-Lactate may be potentially a useful strategy for the repression of hypoxic response mediated by NDRG3. The threedimensional (3D) structure of NDRG3 was built by using homology modeling for its crystal structure was not available. Then, L-Lactate was docked into NDRG3, from which we knew it bound with amino acid residues Gln69, His183, Asn189, Ala72 and Pro66 of NDRG3 in the most possible active sites. Approximately 3000 compounds have been virtually screened and the 6 topranked compounds were selected as reference molecules to analyze their interaction relationships, which illustrated that some of them might form electrostatic interaction with Glu70 and Asp187, π-&π stack with Phe75 and Tyr180, hydrogen bonds with Gly71 and Asn189, hydrophobic effect with Ala72 and Ile184. Results: Novel molecules were designed through structural optimization of the 6 top-ranked compounds and subsequently their ADMET properties were predicted. Conclusion: These molecules may be potential drug candidates for the suppression of hypoxic response mediated by NDRG3 and targeted therapy for hypoxia-induced diseases.

The clpB gene of Bifidobacterium breve UCC 2003: transcriptional analysis and first insights into stress induction

Microbiology ◽  
2005 ◽  
Vol 151 (9) ◽  
pp. 2861-2872 ◽  
Author(s):  
Marco Ventura ◽  
John G. Kenny ◽  
Ziding Zhang ◽  
Gerald F. Fitzgerald ◽  
Douwe van Sinderen
Keyword(s):  
3D Structure ◽  
Binding Mode ◽  
Dna Interaction ◽  
Transcriptional Analysis ◽  
Amino Acid Residues ◽  
Mobility Shift ◽  
Bifidobacterium Breve ◽  
Gel Mobility Shift ◽  
Slot Blot Analysis

The so-called clp genes, which encode components of the Clp proteolytic complex, are widespread among bacteria. The Bifidobacterium breve UCC 2003 genome contains a clpB gene with significant homology to predicted clpB genes from other members of the Actinobacteridae group. The heat- and osmotic-inducibility of the B. breve UCC 2003 clpB homologue was verified by slot-blot analysis, while Northern blot and primer extension analyses showed that the clpB gene is transcribed as a monocistronic unit with a single promoter. The role of a hspR homologue, known to control the regulation of clpB and dnaK gene expression in other high G+C content bacteria was investigated by gel mobility shift assays. Moreover the predicted 3D structure of HspR provides further insight into the binding mode of this protein to the clpB promoter region, and highlights the key amino acid residues believed to be involved in the protein–DNA interaction.

scholarly journals Investigation of major amino acid residues of anti-norfloxacin monoclonal antibodies responsible for binding with fluoroquinolones

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patamalai Boonserm ◽  
Songchan Puthong ◽  
Thanaporn Wichai ◽  
Sajee Noitang ◽  
Pongsak Khunrae ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Amino Acid ◽  
3D Structure ◽  
Cross Reactivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Amino Acid Residues ◽  
Variable Regions ◽  
Complementarity Determining Regions ◽  
Crucial Part ◽  
Major Amino Acid

AbstractIt is important to understand the amino acid residues that govern the properties of the binding between antibodies and ligands. We studied the binding of two anti-norfloxacins, anti-nor 132 and anti-nor 155, and the fluoroquinolones norfloxacin, enrofloxacin, ciprofloxacin, and ofloxacin. Binding cross-reactivities tested by an indirect competitive enzyme-linked immunosorbent assay indicated that anti-nor 132 (22–100%) had a broader range of cross-reactivity than anti-nor 155 (62–100%). These cross-reactivities correlated with variations in the numbers of interacting amino acid residues and their positions. Molecular docking was employed to investigate the molecular interactions between the fluoroquinolones and the monoclonal antibodies. Homology models of the heavy chain and light chain variable regions of each mAb 3D structure were docked with the fluoroquinolones targeting the crucial part of the complementarity-determining regions. The fluoroquinolone binding site of anti-nor 155 was a region of the HCDR3 and LCDR3 loops in which hydrogen bonds were formed with TYR (H:35), ASN (H:101), LYS (H:106), ASN (L:92), and ASN (L:93). These regions were further away in anti-nor 132 and could not contact the fluoroquinolones. Another binding region consisting of HIS (L:38) and ASP (H:100) was found for norfloxacin, enrofloxacin, and ciprofloxacin, whereas only ASP (H:100) was found for ofloxacin.

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