Homology modeling and molecular docking studies of Drosophila and Aedes sex peptide receptors

Kim, Jeong-hyun; Kim, Soo‐Kyung; Lee, Jae-hyuk; Kim, Young-Joon; Goddard, William A.; Kim, Yong-Chul

doi:10.1016/j.jmgm.2016.03.014

Cited by 5 publications

(2 citation statements)

References 39 publications

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“…Quantum mechanical methods, such as the density functional theory (DFT) approach, are frequently used in the study of structures, reactions, and molecular properties [42][43][44], but are strictly limited to systems of few hundreds of atoms. In addition, the protein homology modeling has been successfully employed to predict the 3D protein structure, which is essential in many cases when the tertiary or quaternary structure must be studied [45][46][47][48][49].…”

Section: Introductionmentioning

confidence: 99%

The Se…S/N interactions as a possible mechanism of δ-aminolevulinic acid dehydratase enzyme inhibition by organoselenium compounds: A computational study

Nogara

Orian

Rocha

2020

Computational Toxicology

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Organoselenium compounds present many pharmacological properties and are promising drugs. However, toxicological effects associated with inhibition of thiol-containing enzymes, such as the δ-aminolevulinic acid dehydratase (δ-AlaD), have been described. The molecular mechanism(s) by which they inhibit thiol-containing enzymes at the atomic level, is still not well known. The use of computational methods to understand the physical-chemical properties and biological activity of chemicals is essential to the rational design of new drugs. In this work, we propose an in silico study to understand the δ-AlaD inhibition mechanism by diphenyl diselenide (DPDS) and its putative metabolite, phenylseleninic acid (PSA), using δ-AlaD enzymes from Homo sapiens (Hsδ-AlaD), Drosophila melanogaster (Dmδ-AlaD) and Cucumis sativus (Csδ-AlaD). Protein modeling homology, molecular docking, and DFT calculations are combined in this study. According to the molecular docking, DPDS and PSA might bind in the Hsδ-AlaD and Dmδ-AlaD active sites interacting with the cysteine residues by Se … S interactions. On the other hand, the DPDS does not access the active site of the Csδ-AlaD (a non-thiol protein), while the PSA interacts with the amino acids residues from the active site, such as the Lys291. These interactions might lead to the formation of a covalent bond, and consequently, to the enzyme inhibition. In fact, DFT calculations (mPW1PW91/def2TZVP) demonstrated that the selenylamide bond formation is energetically favored. The in silico data showed here are in accordance with previous experimental studies, and help us to understand the reactivity and biological activity of organoselenium compounds. dehydratase (mδ-AlaD) or porphobilinogen synthase (PBGS) (EC 4.2.1.24). Since the δ-AlaD is an important enzyme involved in the porphyrins' synthesis, its inhibition can have toxicological consequences [8][9][10][11]. The δ-AlaD catalyzes the asymmetric condensation of two molecules of 5-aminolevulinic acid (δ-aminolevulinic acid -5-Ala), forming the porphobilinogen (PBG), which is the precursor of porphyrins' synthesis (Fig. 1B). In the enzyme active site, each substrate binds at two different subsites (A and P), leading to the regioselective product PBG. The acetic acid and propanoic acid side-chains of PBG originate from the subsites A and P, respectively [12][13][14]. Porphyrins are essential to living beings, particularly to the aerobic life, due to the heme prosthetic group, which is involved in the transport of oxygen (hemoglobin and myoglobin), xenobiotic metabolism (cytochrome P450), protection against peroxides (peroxidases and catalases), and chlorophyll synthesis [13,[15][16][17]. There are two major classes of δ-AlaD: the Zn-dependent enzymes (that are present in mammals, fungi

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Section: Introductionmentioning

confidence: 99%

The Se…S/N interactions as a possible mechanism of δ-aminolevulinic acid dehydratase enzyme inhibition by organoselenium compounds: A computational study

Nogara

Orian

Rocha

2020

Computational Toxicology

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“…By measuring binding forces between mutant receptors and the ligand through atomic force microscopy, they experimentally validated the importance of a 5-residue motif in ECL3 in the receptor-ligand interaction [63]. Similar computational protocols including sequence and phylogeny analyses, protein structure prediction, protein-ligand docking, and sometimes ligand redesign were used in other studies for arthropod GPCRs [19,64–66]. In the absence of crystal structures these studies point to the power of computational biology, especially when combined with structure-activity relationship (SAR) experiments (including receptor mutagenesis), in studying GPCR-ligand binding and for designing ligands.…”

Section: Omics Informs Computational Biology In Absence Of Crystal Stmentioning

confidence: 99%

G protein-coupled receptors in arthropod vectors: omics and pharmacological approaches to elucidate ligand-receptor interactions and novel organismal functions

Pietrantonio

Xiong²,

Nachman

et al. 2018

Current Opinion in Insect Science

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Regulation of many physiological processes in animals, certainly those controlled by neuropeptide hormones, involves G protein-coupled receptors (GPCRs). Our work focusing on endocrine regulation of diuresis and water balance in mosquitoes and ticks started in 1997 with the kinin receptor, at the dawn of the omics era. After the genomic revolution, we began work on the endocrinology of reproduction in the red imported fire ant. We will use the template of this comparative work to summarize key points about GPCRs and signaling, and emphasize the most recent developments in the pharmacology of arthropod neuropeptide GPCRs. We will discuss omics’ contributions to the advancement of this field, and its influence on peptidomimetic design while emphasizing work on blood feeding arthropods.

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Knocking down the sex peptide receptor by dsRNA feeding results in reduced oviposition rate in olive fruit flies

Gregoriou

Mathiopoulos

2020

Arch Insect Biochem Physiol

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Insect pests can cause crop damage in yield or quality, resulting in profit losses for farmers. The primary approach to control them is still the use of chemical pesticides resulting in significant hazards to the environment and human health. Biological control and the sterile insect technique are alternative strategies to improve agriculture protection. However, both strategies have significant limitations. A newly introduced approach that could be both effective and species‐specific is the RNA interference mechanism. One key point for the success of this strategy is the delivery method of double‐strand RNA (dsRNA) to the insects. A method of dsRNA delivery to insects with potential use in the field is the oral delivery, feeding the insects engineered microorganisms that produce dsRNA. Here, we present the first protocol for dsRNA feeding using modified bacteria, in the olive fruit fly, the most important insect pest of cultivated olives. We chose to target the sex peptide receptor gene. The sex peptide receptor interacts with the sex peptide, a peptide that is responsible for the postmating behavior in the model organism, Drosophila melanogaster. Feeding the female olive fruit fly with bacteria that produced dsRNA for the sex peptide receptor gene resulted in the development of female insects with significantly lower oviposition rates. Administration of dsRNA producing bacteria in insect diet against target genes that lead to genetic sexing or female‐specific lethality could be added in the armory of control methods.

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Homology modeling and molecular docking studies of Drosophila and Aedes sex peptide receptors

Cited by 5 publications

References 39 publications

The Se…S/N interactions as a possible mechanism of δ-aminolevulinic acid dehydratase enzyme inhibition by organoselenium compounds: A computational study

The Se…S/N interactions as a possible mechanism of δ-aminolevulinic acid dehydratase enzyme inhibition by organoselenium compounds: A computational study

G protein-coupled receptors in arthropod vectors: omics and pharmacological approaches to elucidate ligand-receptor interactions and novel organismal functions

Knocking down the sex peptide receptor by dsRNA feeding results in reduced oviposition rate in olive fruit flies

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