scholarly journals Structural and functional analysis of Hydra Actinoporin-Like Toxin 1 (HALT-1)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
De-Sheng Ker ◽  
Hong Xi Sha ◽  
Mohd Anuar Jonet ◽  
Jung Shan Hwang ◽  
Chyan Leong Ng
Keyword(s):  
Structural Similarity ◽  
Structural Features ◽  
Lipid Binding ◽  
Sea Anemone ◽  
Head Group ◽  
Amino Acid Residues ◽  
Sea Anemones ◽  
Recognition Mechanism ◽  
Structure Comparison ◽  
Hydra Magnipapillata

AbstractActinoporins are a family of α-pore-forming toxins (α-PFTs) that have been identified in sea anemones. Recently, a freshwater Hydra Actinoporin-Like Toxin (HALT) gene family was found in Hydra magnipapillata. Unlike sea anemone actinoporins that use sphingomyelin as their main recognition target, the HALTs proteins may recognise alternative lipid molecules as their target. To unveil the structural insights into lipid preference of HALTs protein as compared to sea anemone actinoporins, we have determined the first crystal structure of actinoporin-like toxin, HALT-1 at 1.43 Å resolution with an acetylated lysine residue K76. Despite the overall structure of HALT-1 sharing a high structural similarity to sea anemone actinoporins, the atomic resolution structure revealed several unique structural features of HALT-1 that may influence the lipid preference and oligomerisation interface. The HALT-1 contains a RAG motif in place of the highly conserved RGD motif found in sea anemone actinoporins. The RAG motif contributed to a sharper β9-β10 turn, which may sway its oligomerisation interface in comparison to sea anemone actinoporins. In the lipid-binding region, the HALT-1 contains a shorter α2 helix and a longer α2-β9 loop due to deletion and subsequently an insertion of five amino acid residues in comparison to the sea anemone actinoporins. Structure comparison and molecular docking analysis further revealed that the HALT-1 lipid-binding site may favour sphingolipids with sulfate or phosphate head group more than the sphingomyelin. The structure of HALT-1 reported here provides a new insight for a better understanding of the evolution and lipid recognition mechanism of actinoporin.

scholarly journals Structure and ligand binding of As-p18, an extracellular fatty acid binding protein from the eggs of a parasitic nematode

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Marina Ibáñez-Shimabukuro ◽  
M. Florencia Rey-Burusco ◽  
Mads Gabrielsen ◽  
Gisela R. Franchini ◽  
Alan Riboldi-Tunnicliffe ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Proteins ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Structural Features ◽  
Lipid Binding ◽  
Head Group ◽  
Resonance Spectroscopy ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

AbstractIntracellular lipid-binding proteins (iLBPs) of the fatty acid-binding protein (FABP) family of animals transport, mainly fatty acids or retinoids, are confined to the cytosol and have highly similar 3D structures. In contrast, nematodes possess fatty acid-binding proteins (nemFABPs) that are secreted into the perivitelline fluid surrounding their developing embryos. We report structures of As-p18, a nemFABP of the large intestinal roundworm Ascaris suum, with ligand bound, determined using X-ray crystallography and nuclear magnetic resonance spectroscopy. In common with other FABPs, As-p18 comprises a ten β-strand barrel capped by two short α-helices, with the carboxylate head group of oleate tethered in the interior of the protein. However, As-p18 exhibits two distinctive longer loops amongst β-strands not previously seen in a FABP. One of these is adjacent to the presumed ligand entry portal, so it may help to target the protein for efficient loading or unloading of ligand. The second, larger loop is at the opposite end of the molecule and has no equivalent in any iLBP structure yet determined. As-p18 preferentially binds a single 18-carbon fatty acid ligand in its central cavity but in an orientation that differs from iLBPs. The unusual structural features of nemFABPs may relate to resourcing of developing embryos of nematodes.

Homology Modeling of Mus Musculus CDK5 and Molecular Docking Studies with Flavonoids

2017 ◽  
Vol 9 (6) ◽  
Author(s):  
Sowmya Suri ◽  
Rumana Waseem ◽  
Seshagiri Bandi ◽  
Sania Shaik
Keyword(s):  
Molecular Docking ◽  
3D Model ◽  
Structural Features ◽  
Docking Studies ◽  
Amino Acid Residues ◽  
Cyclin Dependent Kinase ◽  
Ligand Complex ◽  
Ligand Interaction ◽  
Molecular Docking Studies ◽  
Cyclin Dependent Kinase 5

A 3D model of Cyclin-dependent kinase 5 (CDK5) (Accession Number: Q543f6) is generated based on crystal structure of P. falciparum PFPK5-indirubin-5-sulphonate ligand complex (PDB ID: 1V0O) at 2.30 Å resolution was used as template. Protein-ligand interaction studies were performed with flavonoids to explore structural features and binding mechanism of flavonoids as CDK5 (Cyclin-dependent kinase 5) inhibitors. The modelled structure was selected on the basis of least modeler objective function. The model was validated by PROCHECK. The predicted 3D model is reliable with 93.0% of amino acid residues in core region of the Ramachandran plot. Molecular docking studies with flavonoids viz., Diosmetin, Eriodictyol, Fortuneletin, Apigenin, Ayanin, Baicalein, Chrysoeriol and Chrysosplenol-D with modelled protein indicate that Diosmetin is the best inhibitor containing docking score of -8.23 kcal/mol. Cys83, Lys89, Asp84. The compound Diosmetin shows interactions with Cys83, Lys89, and Asp84.

Biological and In silico Studies on Synthetic Analogues of Tyrosine Betaine as Inhibitors of Neprilysin - A Drug Target for the Treatment of Heart Failure

2018 ◽  
Vol 24 (17) ◽  
pp. 1899-1904
Author(s):  
Daniel Fabio Kawano ◽  
Marcelo Rodrigues de Carvalho ◽  
Mauricio Ferreira Marcondes Machado ◽  
Adriana Karaoglanovic Carmona ◽  
Gilberto Ubida Leite Braga ◽  
...  
Keyword(s):  
Heart Failure ◽  
Secondary Metabolites ◽  
Structural Similarity ◽  
Structural Features ◽  
Major Constituent ◽  
Binding Modes ◽  
Starting Point ◽  
In Silico Studies ◽  
Nep Inhibition

Background: Fungal secondary metabolites are important sources for the discovery of new pharmaceuticals, as exemplified by penicillin, lovastatin and cyclosporine. Searching for secondary metabolites of the fungi Metarhizium spp., we previously identified tyrosine betaine as a major constituent. Methods: Because of the structural similarity with other inhibitors of neprilysin (NEP), an enzyme explored for the treatment of heart failure, we devised the synthesis of tyrosine betaine and three analogues to be subjected to in vitro NEP inhibition assays and to molecular modeling studies. Results: In spite of the similar binding modes with other NEP inhibitors, these compounds only displayed moderate inhibitory activities (IC50 ranging from 170.0 to 52.9 µM). However, they enclose structural features required to hinder passive blood brain barrier permeation (BBB). Conclusions: Tyrosine betaine remains as a starting point for the development of NEP inhibitors because of the low probability of BBB permeation and, consequently, of NEP inhibition at the Central Nervous System, which is associated to an increment in the Aβ levels and, accordingly, with a higher risk for the onset of Alzheimer's disease.

Towards effective link prediction: A hybrid similarity model

2020 ◽  
pp. 1-14
Author(s):  
Longjie Li ◽  
Lu Wang ◽  
Hongsheng Luo ◽  
Xiaoyun Chen
Keyword(s):  
Link Prediction ◽  
Structural Similarity ◽  
Research Direction ◽  
Structural Features ◽  
Proposed Model ◽  
Similarity Model ◽  
Weight Calculation ◽  
Stable Performance ◽  
Grey Relation ◽  
Important Research Direction

Link prediction is an important research direction in complex network analysis and has drawn increasing attention from researchers in various fields. So far, a plethora of structural similarity-based methods have been proposed to solve the link prediction problem. To achieve stable performance on different networks, this paper proposes a hybrid similarity model to conduct link prediction. In the proposed model, the Grey Relation Analysis (GRA) approach is employed to integrate four carefully selected similarity indexes, which are designed according to different structural features. In addition, to adaptively estimate the weight for each index based on the observed network structures, a new weight calculation method is presented by considering the distribution of similarity scores. Due to taking separate similarity indexes into account, the proposed method is applicable to multiple different types of network. Experimental results show that the proposed method outperforms other prediction methods in terms of accuracy and stableness on 10 benchmark networks.

Gametogenesis and the reproductive cycle in the deep-sea anemone Paracalliactis stephensoni (Cnidaria: Actiniaria)

1990 ◽  
Vol 70 (1) ◽  
pp. 163-172 ◽  
Author(s):  
Michel Praet-Van
Keyword(s):  
Organic Matter ◽  
Shallow Water ◽  
Deep Sea ◽  
Phytoplankton Bloom ◽  
Sea Anemone ◽  
Bay Of Biscay ◽  
Sea Anemones ◽  
Spring Phytoplankton Bloom ◽  
Sea Floor ◽  
Ultrastructural Investigation

This ultrastructural investigation of gametogenesis in a deep-sea anemone of the Bay of Biscay trawled around 2000 m depth, contributes to the knowledge of biology and strategy of reproduction of deep-sea benthos.This sea anemone is dioecious. The sperm appears very similar to those of shallow water sea anemones of the genus, Calliactis. The ultrastructural investigation of oogenesis allows the characteristics of the stages of previtellogenesis and vitellogenesis to be defined. The latter begins with a period of lipogenesis correlated with the formation of a trophonema. Mature oocytes measure up to 180 (im in diameter. Study of spermatogenesis and oogenesis reveals that spawning occurs in April/May. In males, the main area of testicular cysts, full of sperm, reaches maximal development from March to May and, in females, the percentage of mature oocytes decreases from 33% in April to 1% in May.Spawning may be induced by the advent in the deep-sea of the products of the spring phytoplankton bloom. This period of spawning, during the increased deposition of organic matter to the deep-sea floor, may be an advantageous strategy for early development of Paracalliactis.

scholarly journals Multiple Distinct Sets of Stereotyped Antigen Receptors Indicate a Role for Antigen in Promoting Chronic Lymphocytic Leukemia

2004 ◽  
Vol 200 (4) ◽  
pp. 519-525 ◽  
Author(s):  
Bradley T. Messmer ◽  
Emilia Albesiano ◽  
Dimitar G. Efremov ◽  
Fabio Ghiotto ◽  
Steven L. Allen ◽  
...  
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Structural Features ◽  
Lymphocytic Leukemia ◽  
Cell Subpopulation ◽  
Amino Acid Residues ◽  
Antigen Receptors ◽  
Region Gene ◽  
V Region ◽  
Unique Amino Acid

Previous studies suggest that the diversity of the expressed variable (V) region repertoire of the immunoglobulin (Ig)H chain of B-CLL cells is restricted. Although limited examples of marked constraint in the primary structure of the H and L chain V regions exist, the possibility that this level of restriction is a general principle in this disease has not been accepted. This report describes five sets of patients, mostly with unmutated or minimally mutated IgV genes, with strikingly similar B cell antigen receptors (BCRs) arising from the use of common H and L chain V region gene segments that share CDR3 structural features such as length, amino acid composition, and unique amino acid residues at recombination junctions. Thus, a much more striking degree of structural restriction of the entire BCR and a much higher frequency of receptor sharing exists among patients than appreciated previously. The data imply that either a significant fraction of B-CLL cells was selected by a limited set of antigenic epitopes at some point in their development and/or that they derive from a distinct B cell subpopulation with limited Ig V region diversity. These shared, stereotyped Ig molecules may be valuable probes for antigen identification and important targets for cross-reactive idiotypic therapy.

scholarly journals Structural and functional analysis of the Na+/H+ exchanger

2007 ◽  
Vol 401 (3) ◽  
pp. 623-633 ◽  
Author(s):  
Emily R. Slepkov ◽  
Jan K. Rainey ◽  
Brian D. Sykes ◽  
Larry Fliegel
Keyword(s):  
Intracellular Ph ◽  
Sequence Similarity ◽  
Structural Data ◽  
Structural Similarity ◽  
Integral Membrane Protein ◽  
Volume Control ◽  
Amino Acid Residues ◽  
Physiological Processes ◽  
High Resolution Structure ◽  
Extracellular Sodium

The mammalian NHE (Na+/H+ exchanger) is a ubiquitously expressed integral membrane protein that regulates intracellular pH by removing a proton in exchange for an extracellular sodium ion. Of the nine known isoforms of the mammalian NHEs, the first isoform discovered (NHE1) is the most thoroughly characterized. NHE1 is involved in numerous physiological processes in mammals, including regulation of intracellular pH, cell-volume control, cytoskeletal organization, heart disease and cancer. NHE comprises two domains: an N-terminal membrane domain that functions to transport ions, and a C-terminal cytoplasmic regulatory domain that regulates the activity and mediates cytoskeletal interactions. Although the exact mechanism of transport by NHE1 remains elusive, recent studies have identified amino acid residues that are important for NHE function. In addition, progress has been made regarding the elucidation of the structure of NHEs. Specifically, the structure of a single TM (transmembrane) segment from NHE1 has been solved, and the high-resolution structure of the bacterial Na+/H+ antiporter NhaA has recently been elucidated. In this review we discuss what is known about both functional and structural aspects of NHE1. We relate the known structural data for NHE1 to the NhaA structure, where TM IV of NHE1 shows surprising structural similarity with TM IV of NhaA, despite little primary sequence similarity. Further experiments that will be required to fully understand the mechanism of transport and regulation of the NHE1 protein are discussed.

scholarly journals Positively charged amino acid residues located similarly in sea anemone and scorpion toxins

1994 ◽  
Vol 269 (24) ◽  
pp. 16785-16788
Author(s):  
E.P. Loret ◽  
R.M. del Valle ◽  
P. Mansuelle ◽  
F. Sampieri ◽  
H. Rochat
Keyword(s):  
Amino Acid ◽  
Sea Anemone ◽  
Amino Acid Residues ◽  
Scorpion Toxins ◽  
Positively Charged

The Behaviour and Neuromuscular System of Gonactinia Prolifera, A Swimming Sea-Anemone

1971 ◽  
Vol 55 (3) ◽  
pp. 611-640
Author(s):  
ELAINE A. ROBSON
Keyword(s):  
Electrical Stimulation ◽  
Mechanical Stimulation ◽  
Motor Units ◽  
Nerve Cells ◽  
Sea Anemone ◽  
Neuromuscular System ◽  
Sea Anemones ◽  
Nerve Net ◽  
Local Contraction ◽  
Electric Shocks

1. In Gonactinia well-developed ectodermal muscle and nerve-net extend over the column and crown and play an important part in the anemone's behaviour. 2. Common sequences of behaviour are described. Feeding is a series of reflex contractions of different muscles by means of which plankton is caught and swallowed. Walking, in the form of brief looping steps, differs markedly in that it continues after interruptions. Anemones also swim with rapid tentacle strokes after contact with certain nudibranch molluscs, strong mechanical disturbance or electrical stimulation. 3. Swimming is attributed to temporary excitation of a diffuse ectodermal pacemaker possibly situated in the upper column. 4. From the results of electrical and mechanical stimulation it is concluded that the endodermal neuromuscular system resembles that of other anemones but that the properties of the ectodermal neuromuscular system require a new explanation. The size and spread of responses to electric shocks vary with intensity, latency is variable and there is a tendency to after-discharge. There is precise radial localization, for example touching a tentacle or the column causes it to bend towards or away from the stimulus. 5. A model to explain these and other features includes multipolar nerve cells closely linked to the nerve-net which would act as intermediate motor units, causing local contraction of the ectodermal muscle. This scheme can be applied to other swimming anemones but there is no evidence that it holds for sea anemones generally.

scholarly journals Structural Similarities and Differences between Two Functionally Distinct SecA Proteins, Mycobacterium tuberculosis SecA1 and SecA2

2015 ◽  
Vol 198 (4) ◽  
pp. 720-730 ◽  
Author(s):  
Stephanie Swanson ◽  
Thomas R. Ioerger ◽  
Nathan W. Rigel ◽  
Brittany K. Miller ◽  
Miriam Braunstein ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Signal Peptide ◽  
Protein A ◽  
Structural Difference ◽  
Structural Similarity ◽  
Structural Features ◽  
Dominant Negative ◽  
Content Type ◽  
Functional Regions ◽  
Suppressor Mutations

ABSTRACTWhile SecA is the ATPase component of the major bacterial secretory (Sec) system, mycobacteria and some Gram-positive pathogens have a second paralog, SecA2. In bacteria with two SecA paralogs, each SecA is functionally distinct, and they cannot compensate for one another. Compared to SecA1, SecA2 exports a distinct and smaller set of substrates, some of which have roles in virulence. In the mycobacterial system, some SecA2-dependent substrates lack a signal peptide, while others contain a signal peptide but possess features in the mature protein that necessitate a role for SecA2 in their export. It is unclear how SecA2 functions in protein export, and one open question is whether SecA2 works with the canonical SecYEG channel to export proteins. In this study, we report the structure ofMycobacterium tuberculosisSecA2 (MtbSecA2), which is the first structure of any SecA2 protein. A high level of structural similarity is observed between SecA2 and SecA1. The major structural difference is the absence of the helical wing domain, which is likely to play a role in howMtbSecA2 recognizes its unique substrates. Importantly, structural features critical to the interaction between SecA1 and SecYEG are preserved in SecA2. Furthermore, suppressor mutations of a dominant-negativesecA2mutant map to the surface of SecA2 and help identify functional regions of SecA2 that may promote interactions with SecYEG or the translocating polypeptide substrate. These results support a model in which the mycobacterial SecA2 works with SecYEG.IMPORTANCESecA2 is a paralog of SecA1, which is the ATPase of the canonical bacterial Sec secretion system. SecA2 has a nonredundant function with SecA1, and SecA2 exports a distinct and smaller set of substrates than SecA1. This work reports the crystal structure of SecA2 ofMycobacterium tuberculosis(the first SecA2 structure reported for any organism). Many of the structural features of SecA1 are conserved in the SecA2 structure, including putative contacts with the SecYEG channel. Several structural differences are also identified that could relate to the unique function and selectivity of SecA2. Suppressor mutations of asecA2mutant map to the surface of SecA2 and help identify functional regions of SecA2 that may promote interactions with SecYEG.

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